Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.

An experimental investigation of the stereocamera's systematic error is carried out to optimize three-dimensional (3-D) dust observation on the HL-2A tokamak. It is found that a larger 3-D region occupied by all calibration points is able to reduce the 3-D reconstruction systematic error of the stereocamera. In addition, the 3-D reconstruction is the most accurate around the region where the calibration points are located. Based on these experimental results, the design of the stereocamera on the HL-2A tokamak is presented, and a set of practical procedures to optimize the 3-D reconstruction accuracy of the stereocamera are proposed.

Previous studies have reported inconsistent associations between low-carbohydrate diets (LCD) and plasma lipid profile. Also, there is little evidence on the role of the quality and food sources of macronutrients in LCD in cardiometabolic health. We investigated the cross-sectional associations between LCD and plasma cardiometabolic risk markers in a nationwide representative sample of the US population. Diet was measured through two 24-h recalls. Overall, healthy (emphasising unsaturated fat, plant protein and less low-quality carbohydrates) and unhealthy (emphasising saturated fat, animal protein and less high-quality carbohydrate) LCD scores were developed according to the percentage of energy as total and subtypes of carbohydrate, protein and fat. Linear regression was used to estimate the percentage difference of plasma marker concentrations by LCD scores. A total of 34 785 participants aged 18–85 years were included. After adjusting for covariates including BMI, healthy LCD was associated with lower levels of insulin, homoeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP) and TAG, and higher levels of HDL-cholesterol, with the percentage differences (comparing extreme quartile of LCD score) of −5·91, −6·16, −9·13, −9·71 and 7·60 (all P trend < 0·001), respectively. Conversely, unhealthy LCD was associated with higher levels of insulin, HOMA-IR, CRP and LDL-cholesterol (all P trend < 0·001). Our results suggest that healthy LCD may have positive, whereas unhealthy LCD may have negative impacts on CRP and metabolic and lipid profiles. These findings underscore the need to carefully consider the quality and subtypes of macronutrients in future LCD studies.

Embryo quality determines the success of in vitro fertilization and embryo transfer (IVF-ET) treatment. Biomarkers for the evaluation of embryo quality have some limitations. Apoptosis in cumulus cells (CCs) is important for ovarian function. PTEN (phosphatase and tensin homolog) is a well known tumour suppressor gene that functions as a mediator of apoptosis and is crucial for mammalian reproduction. In the present study, we analyzed the expression level of PTEN in human CCs and aimed to investigate its association with embryo developmental competence in IVF treatment cycles. The PTEN mRNA level in CCs was measured using real-time fluorescence quantitative PCR. The association of the differential expression of PTEN with embryo quality was analyzed. Our data showed that PTEN mRNA levels were significantly decreased in CCs surrounding mature oocytes compared with immature oocytes. Similar changes were found in the analysis of fertilization and blastocyst formation. The speculation that the measurement of PTEN mRNA levels in human CCs would provide a useful tool for selecting oocytes with greater chances to implant into the uterus needs to be further verified through single-embryo transfer in the future. The proapoptotic mechanism of PTEN in human reproduction needs to be further studied.

Applying non-accident critical events (NACEs) as an alternative measuring method to assess ship collision risk has become popular in recent years. NACEs has shown temporal features in different waters. This study uses the quaternion ship domain method to identify NACEs around the Yangtze Estuary and adjacent coastal waters from the Automatic Identification System (AIS) data in October 2019. The results indicate that NACEs show different temporal features in estuaries and coastal waters. The relationship between tides, channel types and ships is discussed. In addition, we established a statistical method for the occurrence time of NACEs and the state of tides according to the half-tide level and the nearest time. The outcomes of this study provide a direction for exploring the relationship between NACEs and environmental conditions, which is also instructive for the study of the causes of ship accidents.

Extensive magmatism in NE China, eastern Central Asian Orogenic Belt, has produced multi-stage granitic plutons and accompanying W mineralization. The Narenwula complex in the southwestern Great Xing’an Range provides important insights into the petrogenesis, geodynamic processes and relationship with W mineralization. The complex comprises granodiorites, monzogranites and granite porphyry. Mafic microgranular enclaves are common in the granodiorites, and have similar zircon U–Pb ages as their host rocks (258.5–253.9 Ma), whereas the W-bearing granitoids yield emplacement ages of 149.8–148.1 Ma. Permian granodiorites are I-type granites that are enriched in large-ion lithophile elements and light rare earth elements, and depleted in high field strength elements and heavy rare earth elements. Both the mafic microgranular enclaves and granodiorites have nearly identical zircon Hf isotopic compositions. The results suggest that the mafic microgranular enclaves and granodiorites formed by the mixing of mafic and felsic magmas. W-bearing granitoids are highly fractionated A-type granites, enriched in Rb, Th, U and Pb, and depleted in Ba, Sr, P, Ti and Eu. They have higher W concentrations and Rb/Sr ratios, and lower Nb/Ta, Zr/Hf and K/Rb ratios than the W-barren granodiorites. These data and negative ϵHf(t) values (–6.0 to –2.1) suggest that they were derived from the partial melting of ancient lower crust and subsequently underwent extreme fractional crystallization. Based on the regional geology, we propose that the granodiorites were generated in a volcanic arc setting related to the subduction of the Palaeo-Asian Ocean, whereas the W-bearing granitoids and associated deposits formed in a post-orogenic extensional setting controlled by the Mongol–Okhotsk Ocean and Palaeo-Pacific Ocean tectonic regimes.

The efficiency of establishing pig pluripotent embryonic stem cell clones from blastocysts is still low. The transcription factor Nanog plays an important role in maintaining the pluripotency of mouse and human embryonic stem cells. Adequate activation of Nanog has been reported to increase the efficiency of establishing mouse embryonic stem cells from 3.5 day embryos. In mouse, Nanog starts to be strongly expressed as early as the morula stage, whereas in porcine NANOG starts to be strongly expressed by the late blastocyst stage. Therefore, here we investigated both the effect of expressing NANOG on porcine embryos early from the morula stage and the efficiency of porcine pluripotent embryonic stem cell clone formation. Compared with intact porcine embryos, NANOG overexpression induced a lower blastocyst rate, and did not show any advantages for embryo development and pluripotent embryonic stem cell line formation. These results indicated that, although NANOG is important pluripotent factor, NANOG overexpression is unnecessary for the initial formation of porcine pluripotent embryonic stem cell clones in vitro.

Hyperinsulinaemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinaemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinaemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-h recalls. Two empirical dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinaemia (C-peptide and insulin) and insulin resistance (homoeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until 31 December 2015 were identified by the National Death Index. Multivariable hazard ratios (HR) and 95 % CI were calculated using Cox regression models. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants. For EDIH, the multivariable-adjusted HR (comparing extreme quintiles) were 1·20 (95 % CI 1·09, 1·32, P-trend<0·001) for overall mortality and 1·41 (95 % CI 1·15, 1·74, P-trend = 0·002) for CVD mortality. Similar associations were observed for EDIR with HR of 1·18 (95 % CI 1·07, 1·29, P-trend < 0·001) for total and 1·35 (95 % CI 1·09, 1·67, P-trend = 0·005) for CVD mortality. After further adjustments for BMI and diabetes, these positive associations were somewhat attenuated. Our findings suggested that diets with higher insulinaemic potential are associated with increased risk of overall and CVD-specific mortality.

Several candidates of universal influenza vaccine (UIV) have entered phase III clinical trials, which are expected to improve the willingness and coverage of the population substantially. The impact of UIV on the seasonal influenza epidemic in low influenza vaccination coverage regions like China remains unclear. We proposed a new compartmental model involving the transmission of different influenza subtypes to evaluate the effects of UIV. We calibrated the model by weekly surveillance data of influenza in Xi'an City, Shaanxi Province, China, during 2010/11–2018/19 influenza seasons. We calculated the percentage of averted infections under 2-month (September to October) and 6-month (September to the next February) vaccination patterns with varied UIV effectiveness and coverage in each influenza season, compared with no UIV scenario. A total of 195 766 influenza-like illness (ILI) cases were reported during the nine influenza seasons (2010/11–2018/19), of which the highest ILI cases were among age group 0–4 (59.60%) years old, followed by 5–14 (25.22%), 25–59 (8.19%), 15–24 (3.75%) and ⩾60 (3.37%) years old. The influenza-positive rate for all age groups among ILI cases was 17.51%, which is highest among 5–14 (23.75%) age group and followed by 25–59 (16.44%), 15–24 (16.42%), 0–4 (14.66%) and ⩾60 (13.98%) age groups, respectively. Our model showed that UIV might greatly avert influenza infections irrespective of subtypes in each influenza season. For example, in the 2018/19 influenza season, 2-month vaccination pattern with low UIV effectiveness (50%) and coverage (10%), and high UIV effectiveness (75%) and coverage (30%) could avert 41.6% (95% CI 27.8–55.4%) and 83.4% (80.9–85.9%) of influenza infections, respectively; 6-month vaccination pattern with low and high UIV effectiveness and coverage could avert 32.0% (15.9–48.2%) and 74.2% (69.7–78.7%) of influenza infections, respectively. It would need 11.4% (7.9–15.0%) of coverage to reduce half of the influenza infections for 2-month vaccination pattern with low UIV effectiveness and 8.5% (5.0–11.2%) of coverage with high UIV effectiveness, while it would need 15.5% (8.9–20.7%) of coverage for 6-month vaccination pattern with low UIV effectiveness and 11.2% (6.5–15.0%) of coverage with high UIV effectiveness. We conclude that UIV could significantly reduce the influenza infections even for low UIV effectiveness and coverage. The 2-month vaccination pattern could avert more influenza infections than the 6-month vaccination pattern irrespective of influenza subtype and UIV effectiveness and coverage.

Inflammation is a central mechanism in metabolic disorders associated with morbidity and mortality and dietary factors can modulate inflammation. We aimed to prospectively investigate the association between an empirically developed, food-based dietary inflammatory pattern (EDIP) score and the risk of overall and cause-specific mortality, using data from the US National Health and Nutrition Examination Survey from 1999 to 2014. EDIP score was derived by entering thirty-nine predefined commonly consumed food groups into the reduced rank regression models followed by stepwise linear regression, which was most predictive of two plasma inflammation biomarkers including C-reactive protein and leucocyte count among 25 500 US adults. This score was further validated in a testing set of 9466 adults. Deaths from baseline until 31 December 2015 were identified through record linkage to the National Death Index. During a median follow-up of 7·8 years among 40 074 participants, we documented 4904 deaths. Compared with participants in the lowest quintile of EDIP score, those in the highest quintile had a higher risk of overall death (hazard ratio (HR) = 1·19, 95 % CI 1·08, 1·32, Ptrend = 0·002), and deaths from cancer (HR = 1·41, 95 % CI 1·14, 1·74, Ptrend = 0·017) and CVD (HR = 1·22, 95 % CI 0·98, 1·53, Ptrend = 0·211). When stratified by age, the association of EDIP with overall mortality was stronger among individuals under 65 years of age (Pinteraction = 0·001). Diets with a higher inflammatory potential were associated with increased risk of overall and cancer-specific mortality. Interventions to reduce the adverse effect of pro-inflammatory diets may potentially promote health and longevity.

The Songling and Majiayu peridotite blocks occur in the Eastern Block, North China Craton (NCC). Geothermobarometry data show that the Songling peridotites began exhumation from a depth of c. 70 km (c. 23 kbar). During exhumation, the Songling peridotites were intruded by an upper-crust-derived, high-δ18O (up to +7.28‰ in zircon) trondhjemitic dyke at 2.47 Ga and experienced granulite-facies metamorphism. The Songling peridotites have hybrid mantle wedge (HMW) -like high SiO2 (> 45 wt%), high FeOt (c. 10 wt%) content, high modal orthopyroxene abundance (> 35%) and high ϵNd(t) (+18.4 to +21.4), which were generated by the reaction between peridotite and eclogite-derived melts. The clinopyroxenes from the Songling peridotites were in equilibrium with a Nb-, Zr- and Ti-depleted arc-like magma. The Majiayu peridotites are characterized by depletion of Nb, Zr and Hf and are highly enriched in FeOt, Th and light rare earth elements (LREEs), which can be interpreted as an open system reaction between hydrous melts and fore-arc mantle peridotites. These two peridotite blocks are considered to be arc-related mantle peridotites that experienced melt extraction and metasomatism in different styles. They were exhumed to the north margin of the North China Craton during the c. 2.47 Ga arc–continent collision along the Zunhua structural belt.

Manganese (Mn) oxides have been prevalent on Earth since before the Great Oxidation Event and the Mn cycle is one of the most important biogeochemical processes on the Earth's surface. In sunlit natural environments, the photochemistry of Mn oxides has been discovered to enable solar energy harvesting and conversion in both geological and biological systems. One of the most widespread Mn oxides is birnessite, which is a semiconducting layered mineral that actively drives Mn photochemical cycling in Nature. The oxygen-evolving centre in biological photosystem II (PSII) is also a Mn-cluster of Mn4CaO5, which transforms into a birnessite-like structure during the photocatalytic oxygen evolution process. This phenomenon draws the potential parallel of Mn-functioned photoreactions between the organic and inorganic world. The Mn photoredox cycling involves both the photo-oxidation of Mn(II) and the photoreductive dissolution of Mn(IV/III) oxides. In Nature, the occurrence of Mn(IV/III) photoreduction is usually accompanied with the oxidative degradation of natural organics. For Mn(II) oxidation into Mn oxides, mechanisms of biological catalysis mediated by microorganisms (such as Pseudomonas putida and Bacillus species) and abiotic photoreactions by semiconducting minerals or reactive oxygen species have both been proposed. In particular, anaerobic Mn(II) photo-oxidation processes have been demonstrated experimentally, which shed light on Mn oxide emergence before atmospheric oxygenation on Earth. This review provides a comprehensive and up-to-date elaboration of Mn oxide photoredox cycling in Nature, and gives brand-new insight into the photochemical properties of semiconducting Mn oxides widespread on the Earth's surface.

The dynamical stability of the cable-driven lower-limb rehabilitation training robot (CLLRTR) is a crucial question. Based on the established dynamics model of CLLRTR, the solution to the wrench closure of the under-constrained system is presented. Secondly, the stability index of CLLRTR is proposed by the Krasovski method. Finally, in order to analyze the stability distribution of CLLRTR in the workspace, the stability evaluation index in the workspace is calculated using the eigenvalue decomposition method. The stability distribution laws of CLLRTR are further verified by the experimental study. The results provide references for studying trajectory planning and anti-pendulum control of CLLRTR.

Fractal features of the turbulent/non-turbulent interface (TNTI) in shock wave/turbulent boundary-layer interaction (SWBLI) flows are essential in understanding the physics of the SWBLI and the supersonic turbulent boundary layer, yet have received almost no attention previously. Accordingly, this study utilises a high spatiotemporal resolution visualisation technique, ice-cluster-based planar laser scattering (IC-PLS), to acquire the TNTI downstream of the reattachment in a SWBLI flow. Evolution of the fractal features of the TNTI in this SWBLI flow is analysed by comparing the parameters of the TNTI acquired in this study with those from a previous result (Zhuang et al.J. Fluid Mech., vol. 843, 2018a).

The following paper investigates the prevalence and characteristics of asymptomatic norovirus infection in the population living around oyster farm sites. Two consecutive surveys were conducted from January 2014 to December 2014 and 4549 stool samples were screened during the same time period. The total asymptomatic infection rate was 4.04% (184/4549). Norovirus infection rate was 5.20% in oyster farming population which was significantly higher compared with non-farming population where the infection rate was 3.65% (χ2 = 5.49, P < 0.05). A total of 184 NoV positive samples were identified by real time-quantitative polymerase chain reaction (RT-qPCR) and semi-nested RT-PCR and 136 sequences were obtained. The sequences were clustered into 14 genotypes. GI strains were clustered into six genotypes, including GI.2, GI.3, GI.5, GI.6, GI.8 and GI.9; while GII strains were clustered into GII.2, GII.3, GII.4, GII.5, GII.6, GII.8 and GII.13. GI.9 and GII.17 were the predominant and most prevalent genotypes, respectively. The GII.17 genotype replaced GII.4 becoming the dominant genotype in the oyster farming area in 2014. To sum up, long-term monitoring of asymptomatic infection is crucial for the detection of new variant strains and for identifying outbreaks during the early stage.

To solve extended acquisition time issues inherent in the conventional hopping-scanning mode of scanning ion-conductance microscopy (SICM), a new transverse-fast scanning mode (TFSM) is proposed. Because the transverse motion in SICM is not the detection direction and therefore presents no collision problem, it has the ability to move at high speed. In TSFM, the SICM probe gradually descends in the vertical/detection direction and rapidly scans in the transverse/nondetection direction. Further, the highest point that decides the hopping height of each scanning line can be quickly obtained. In conventional hopping mode, however, the hopping height is artificially set without a priori knowledge and is typically very large. Consequently, TFSM greatly improves the scanning speed of the SICM imaging system by effectively reducing the hopping height of each pixel. This study verifies the feasibility of this novel scanning method via theoretical analysis and experimental study, and compares the speed and quality of the scanning images obtained in the TFSM with that of the conventional hopping mode. The experimental results indicate that the TFSM method has a faster scanning speed than other SICM scanning methods while maintaining the quality of the images. Therefore, TFSM provides the possibility to quickly obtain high-resolution three-dimensional topographical images of extremely complex samples.

To assess the changes in the relationship between serum Mg and blood lipids of Chinese adults with type 2 diabetes (T2D) or central obesity, a total of 8163 subjects (mean age 59·6 years, 54·9 % men) were analysed. Participants were classified according to blood Mg (below 0·65 mmol/l, 0·65–0·95 mmol/l and above 0·95 mmol/l), T2D (yes/no) and central obesity (yes/no). Blood lipids (TAG, total cholesterol (TC), HDL-cholesterol and LDL-cholesterol) were determined by standardised methods and conditions. A significant increase in blood lipids, with the exception of HDL-cholesterol, across progressive Mg groups in all subjects was noted (P<0·05). TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with central obesity compared with those without central obesity (P<0·05). A significant increase in TAG, TC and LDL-cholesterol across progressive Mg groups was observed in subjects without T2D (P<0·05). However, no significant change of HDL-cholesterol and LDL-cholesterol across progressive Mg groups was observed in subjects with T2D (P>0·05). TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with T2D than those without T2D (P<0·05). Multivariable models for TAG and LDL-cholesterol failed to attain statistical significance in diabetics, by using a generalised linear or parsimonious model. TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with T2D or central obesity. Blood lipids, with the exception of HDL-cholesterol, were associated with serum Mg, but this association was somehow influenced by T2D in LDL-cholesterol. In addition, multivariable models for both TAG and LDL-cholesterol failed to attain statistical significance among subjects with T2D, different from subjects without T2D.

To investigate the effects of heat stress on broiler metabolism, we assigned 144 broilers to normal control (NC), heat stress (HS) or pair-fed (PF) groups and then monitored the effects using growth performance, carcass characteristics, biochemical assays and GC-MS-based metabolomics. The up-regulation of cloacal temperature confirmed that our experiment was successful in inducing chronic heat stress. The average daily gain and average daily feed intake of the HS group were significantly lower than those of the NC group, by 28·76 and 18·42 %, respectively (P<0·001), whereas the feed:gain ratio was significantly higher, by 14·49 % (P=0·003), and heat stress also increased leg proportion (P=0·027) and intramuscular fat proportion (P<0·001) and decreased breast proportion (P=0·009). When comparing the HS and NC groups and HS and PF groups, our metabolomics approach identified seventy-eight and thirty-four metabolites, respectively, with significantly different levels (variable importance in the projection values >1 and P<0·05). The greater feed:gain ratio of the HS group was significantly positively correlated with the leg, abdominal fat, subcutaneous fat and intramuscular fat proportions and levels of some free amino acids (proline, l-cysteine, methionine and threonine) but was negatively correlated with breast proportion and levels of some NEFA (stearic acid, arachidonic acid, palmitic acid and oleic acid). These findings indicated that the heat-stressed broilers were in negative energy balance and unable to effectively mobilise fat, thereby resulting in protein decomposition, which subsequently affected growth performance and carcass characteristics.