The 4.2 ka event is widely presumed to be a globally widespread aridity event and has been linked to several episodes of societal changes across the globe. Whether this climate event impacted the cultural development in south-central China remains uncertain due to a lack of regional paleorainfall records. We present here stalagmite stable carbon isotope and trace element–based reconstruction of hydroclimatic conditions from south-central China. Our data reveal a sub–millennial scale (~5.6 to 4.3 ka) drying trend in the region followed by a gradual transition to wetter conditions during the 4.2 ka event (4.3–3.9 ka). Together with the existing archaeological evidence, our data suggest that the drier climate before 4.3 ka may have promoted the Shijiahe culture, while the pluvial conditions during the 4.2 ka event may have adversely affected its settlements in low-lying areas. While military conflicts with the Wangwan III culture may have accelerated the collapse of Shijiahe culture, we suggest that the joint effects of climate and the region's topography also played important causal roles in its demise.

Lower-crust-derived adakitic rocks in the Gangdese belt provide important constraints on the timing of Tibetan crustal thickening and on the relative contributions of magmatic and tectonic processes. Here we present geochronological and geochemical data for the Wangdui porphyritic monzogranites in the western Gangdese belt. Zircon U–Pb dating yields emplacement ages of 46–44 Ma. All samples have high Sr (321–599 ppm), low Yb (0.76–1.33 ppm) and Y (10.6–18.3 ppm) contents, with high La/Yb (51.1–72.3) and Sr/Y (21.0–51.4) ratios, indicating adakitic affinities. The low MgO (0.97–1.76 wt %), Cr (7.49–53.6 ppm) and Ni (4.75–29.1 ppm) contents, as well as high 87Sr/86Sr(i) (0.7143–0.7145), low ϵNd(t) (−10.4 to −9.8) and zircon ϵHf(t) (−17.7 to 0.4) values, suggest that the Wangdui pluton most likely originated from partial melting of the thickened ancient lower crust. In combination with previously published data, despite the east–west-trending heterogeneity of crustal composition in the Gangdese belt, the La/Yb ratios of magmatic rocks reveal that both western and eastern segments experienced remarkable crustal thickening in the Eocene. However, in contrast to the thickened juvenile lower crust in the eastern segment formed by the underplating of mantle-derived magmas, tectonic shortening plays a more crucial role in thickening of the ancient basement in western Gangdese. In fact, such Eocene-thickened ancient lower-crust-derived adakitic rocks are widely distributed in the central Himalayan–Tibetan orogen. This, together with the extensive development of fold–thrust belts, suggests that tectonic shortening might be the main mechanism accounting for the crustal thickening associated with the India–Asia collision.

The deformation and breakup of droplets in airflows is important in spray and atomisation processes, but the shear effect in non-uniform airflow is rarely reported. In this study, the deformation and breakup of droplets in a shear flow of air is investigated experimentally using high-speed imaging, digital image processing and particle image velocimetry. The results show that in airflow with a strong shear effect, the droplet breakup exhibits unique features due to the uplift and stretching produced by the interaction between the deformed droplet and the shear layer. The breakup process can be divided into three stages according to the droplet morphology and the breakup mechanism, namely the sheet breakup, the swing breakup and the rim breakup stages. Theoretical analysis reveals that the swing breakup is governed by the transverse Rayleigh–Taylor instability. A regime map of the droplet breakup is produced, and the transitions between different regimes are obtained theoretically. The stretching liquid film during the droplet deformation and the fragment size distribution after droplet breakup are analysed quantitatively, and the results show that they are determined by the competition of breakup at different stages affected by the shear. Finally, the effect of the droplet viscosity is investigated, and the viscosity inhibits the droplet breakup in a strong shear airflow.

The decompositions of the skin-friction and heat-transfer coefficients based on the twofold repeated integration in hypersonic transitional and turbulent boundary layers are analysed to give some major reasons of the overshoot phenomena of the wall skin friction and heat transfer. It is shown that the overshoot of the skin-friction coefficient is mainly caused by the drastic change of the mean velocity profiles, especially the strong negative streamwise gradient of the mean streamwise velocity far from the wall; and the overshoot of the heat-transfer coefficient is primarily due to the viscous dissipation, especially the strong positive vertical gradient of the mean streamwise velocity near the wall. These observations are different from the previous observations that the Reynolds shear stress and Reynolds heat flux are the reasons, respectively. Further investigations show that the above observations are independent of the set-up of the wall blowing and suction parameters, which indicates the universality of the major reasons of the overshoot phenomena in our numerical simulations. In the hypersonic turbulent boundary layers, it is observed that the strongly cooled wall temperature and the high Mach number can slightly enhance the contribution of the Reynolds shear stress, and weaken the contribution of the mean convection, mainly due to the strong compressibility effect. Moreover, the magnitudes of the relative contributions of the mean convection, pressure dilatation, viscous dissipation and the Reynolds heat flux increase as the wall temperature increases.

This paper considers a model for oncolytic virotherapy given by the doubly haptotactic cross-diffusion system

\[ \left\{\begin{array}{@{}ll} u_t=D_u\Delta u-\xi_u\nabla\cdot(u\nabla v)+\mu_u u(1-u)-\rho uz,\\ v_t={-} (\alpha_u u+\alpha_w w)v,\\ w_t=D_w\Delta w-\xi_w\nabla\cdot(w\nabla v)- w+\rho uz,\\ z_t=D_z\Delta z-\delta_z z- \rho uz+\beta w, \end{array}\right. \]

$D_u,D_w,D_z,\xi _u,\xi _w,\delta _z,\rho$

$\alpha _u,\alpha _w,\mu _u,\beta$

$\Omega \subset {\mathbb {R}}^{2}$

$\beta <1$

$(u,v,w,z)$

$(1, 0, 0, 0)$

$(L^{\infty }(\Omega ))^{4}$

$t\rightarrow \infty$

Energy homeostasis is essential for organisms to maintain fluctuation in energy accumulation, mobilization. Lipids as the main energy reserve in insects, their metabolism is under the control of many physiological program. This study aimed to determine whether the adipokinetic hormone receptor (AKHR) was involved in the lipid mobilization in the Spodoptera litura. A full-length cDNA encoding AKHR was isolated from S. litura. The SlAKHR protein has a conserved seven-transmembrane domain which is the character of a putative G protein receptor. Expression profile investigation revealed that SlAKHR mRNA was highly expressed in immatural stage and abundant in fat body in newly emerged female adults. Knockdown of SlAKHR expression was achieved through RNAi by injecting double-stranded RNA (dsRNA) into the 6th instar larvae. The content of triacylgycerol (TAG) in the fat body increased significantly after the SlAKHR gene was knockdown. And decrease of TAG releasing to hemolymph with increase of free fatty acid (FFA) in hemolymph were observed when the SlAKHR gene was knowned-down. In addition, lipid droplets increased in fat body was also found. These results suggested that SlAKHR is critical for insects to regulate lipids metabolism.

Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.

Family feasting during the Spring Festival is a Chinese tradition. However, close contact during this period is likely to promote the spread of coronavirus disease 2019 (COVID-19). This study developed a dynamic infectious disease model in which the feast gatherings of families were considered the sole mode of transmission. The model simulates COVID-19 transmission via family feast gatherings through a social contact network. First, a kinship-based, virtual social contact network was constructed, with nodes representing families and connections representing kinships. Families in kinship with each other comprised of the largest globally coupled network, also known as a clique, in which a feast gathering was generated by randomly selecting two or more families willing to gather. The social contact network in the model comprised of 215 cliques formed among 608 families with 1517 family members. The modelling results indicated that when there is only one patient on day 0, the number of new infections will reach a peak on day 29, and almost all families and their members in the social contact network will be infected by day 60. This study demonstrated that COVID-19 can spread rapidly through continuous feast gatherings through social contact networks and that the disease will run rampant throughout the network.

Prospective cohort studies linking organ meat consumption and nonalcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between organ meat consumption and risk of NAFLD in a general Chinese adult population. This prospective cohort study included a total of 15,568 adults who were free of liver disease, cardiovascular disease, and cancer at baseline. Dietary information was collected at baseline using a validated food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between organ meat consumption and risk of NAFLD. During a median of 4.2 years of follow-up, we identified 3,604 incident NAFLD cases. After adjusting for demographic characteristics, lifestyle factors, vegetable, fruit, soft drink, seafood, and red meat consumption, the multivariable hazard ratios (95% confidence intervals) for incident NAFLD across consumption of organ meat were 1.00 (reference) for almost never, 1.04 (0.94, 1.15) for tertile 1, 1.08 (0.99, 1.19) for tertile 2, and 1.11 (1.01, 1.22) for tertile 3, respectively (P for trend <0.05). Such association did not differ substantially in the sensitivity analysis. Our study indicates that organ meat consumption was related to a modestly higher risk of NAFLD among Chinese adults. Further investigations are needed to confirm this finding.

Temperature strongly impacts the rates of physiological and biochemical processes, which in turn can determine the survival and population size of insects. At low temperatures performance is limited, however, cold tolerance and performance at low temperature can be improved after short- or long-term acclimation in many insect species. To understand mechanisms underlying acclimation, we sequenced and compared the transcriptome of the blowfly Chrysomya megacephala under rapid cold hardening (RCH) and long-term cold acclimation (LCA) conditions. The RCH response was dominated by genes related to immune response, spliceosome, and protein processing in endoplasmic reticulum with up-regulation during recovery from RCH. In contrast, LCA was associated with genes related to carbohydrate metabolism and cytoskeleton branching and stabilizing. Meanwhile, mRNA levels of genes related to glycerophospholipid metabolism, and some heat shock proteins (Hsps) were collectively up-regulated by both RCH and LCA. There were more genes and pathway adjustments associated with LCA than RCH. Overall, the transcriptome data provide basic information of molecular mechanisms underpinning the RCH and LCA response. The partly independent molecular responses to RCH and LCA suggest that several avenues for manipulating cold performance exist and RCH might be more effective as it only triggers fewer genes and affects the general metabolisms less. These observations provide some appropriate methods to improve cold tolerance of C. megacephala, and hold promise for developing an extended use of mass-reared C. megacephala with better cold performance as a pollinator of crops at low temperatures.

Evidence of couples’ BMI and its influence on birth weight is limited and contradictory. Therefore, this study aims to assess the association between couple’s preconception BMI and the risk of small for gestational age (SGA)/large for gestational age (LGA) infant, among over 4·7 million couples in a retrospective cohort study based on the National Free Pre-pregnancy Checkups Project (NFPCP) between December 1, 2013 and November 30, 2016 in China. Among the live births, 256,718 (5·44%) SGA events and 506,495 (10·73%) LGA events were documented, respectively. After adjusting for confounders, underweight men had significantly higher risk [OR 1·17 95%CI (1·15-1·19)] of SGA infants compared with men with normal BMI, while a significant and increased risk of LGA infants was obtained for overweight and obese men [OR 1·08 (95% CI: 1·06-1·09); OR 1·19 (95%CI 1·17-1·20)] respectively. The restricted cubic spline (RCS) result revealed a non-linearly decreasing dose-response relationship of paternal BMI (less than 22·64) with SGA. Meanwhile, a non-linearly increasing dose-response relationship of paternal BMI (more than 22·92) with LGA infants was observed. Moreover, similar results about the association between maternal preconception BMI and SGA/LGA infants were obtained. Abnormal preconception BMIs in either women or men were associated with increased risk of SGA/LGA infants, respectively. Overall, couple’s abnormal weight before pregnancy may be an important preventable risk factor for SGA/LGA infants.

The wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Insecticide application is the main method to effectively control wheat aphids. However, CWA has developed resistance to some insecticides due to its extensive application, and understanding resistance mechanisms is crucial for the management of CWA. In our study, a new P450 gene, CYP4CJ6, was identified from CWA and showed a positive response to imidacloprid and thiamethoxam. Transcription of CYP4CJ6 was significantly induced by both imidacloprid and thiamethoxam, and overexpression of CYP4CJ6 in the imidacloprid-resistant strain was also observed. The sensitivity of CWA to these two insecticides was increased after the knockdown of CYP4CJ6. These results indicated that CYP4CJ6 could be associated with CWA resistance to imidacloprid and thiamethoxam. Subsequently, the posttranscriptional regulatory mechanism was assessed, and miR-316 was confirmed to participate in the posttranscriptional regulation of CYP4CJ6. These results are crucial for clarifying the roles of P450 in the resistance of CWA to insecticides.

To achieve autonomous all-day flight by high-altitude long-endurance unmanned aerial vehicle (HALE UAV), a new navigation method with deep integration of strapdown inertial measurement unit (SIMU) and triple star sensors based on atmospheric refraction correction is proposed. By analysing the atmospheric refraction model, the stellar azimuth coordinate system is introduced and the coupling relationship between attitude and position is established. Based on the geometric relationship whereby all the stellar azimuth planes intersect on the common zenith direction, the sole celestial navigation system (CNS) method by stellar refraction with triple narrow fields of view (FOVs) is studied and a loss function is built to evaluate the navigation accuracy. Finally, the new SIMU/triple star sensors deep integrated navigation method with refraction correction upgraded from the traditional inertial navigation system (INS)/CNS integrated method can be established. The results of simulations show that the proposed method can effectively restrain navigation error of a HALE UAV in 24 h steady-state cruising in the stratosphere.

We performed U–Pb dating of detrital zircons and conducted petrological and whole-rock geochemical analyses to assess the provenance of the Upper Triassic – Lower Jurassic clastic rocks in the southeastern margin of the South China Block. Detrital zircon U–Pb ages are mainly classified into age groups of 2000–1700, 900–700, 490–390 and 280–210 Ma, consistent with derivation from the Jiangnan orogenic belt, Nanling Belt, as well as Wuyi and Yunkai domains. Lower Jurassic samples yield a special main age population of 200–190 Ma, and these detrital zircon grains have low Th/U and Nb/Hf ratios and high Th/Nb and Hf/Th ratios, showing they are derived from a continental magmatic arc. However, the cross-correlation and likeness coefficients of kernel density estimates of Upper Triassic and Lower Jurassic sandstones are 0.8608 and 0.8403, indicating that their populations are highly similar. Since the tectonic setting is the key factor in controlling the relationship between source and sink, the stable supply of identical provenance suggests that the tectonic setting did not significantly change during Late Triassic – Early Jurassic time. Sandstone petrography, regional facies distribution and the detrital zircon age patterns all reflect a consistent tectonic setting for the South China Block during Late Triassic – Early Jurassic time. The Palaeo-Pacific subduction therefore did not control the tectonic evolution of the South China Block until after the Early Jurassic Epoch.

We investigated the drug resistance of Mycobacterium tuberculosis isolates from patients with tuberculosis (TB) and HIV, and those diagnosed with only TB in Sichuan, China. TB isolates were obtained from January 2018 to December 2020 and subjected to drug susceptibility testing (DST) to 11 anti-TB drugs and to GeneXpert MTB/RIF testing. The overall proportion of drug-resistant TB (DR-TB) isolates was 32.1% (n = 10 946). HIV testing was not universally available for outpatient TB cases, only 29.5% (3227/10 946) cases had HIV testing results. The observed proportion of multidrug-resistant TB (MDR-TB) isolates was almost double than that of the national level, with approximately 1.5% and 0.1% of the isolates being extensively drug resistant and universally drug resistant, respectively. The proportions of resistant isolates were generally higher in 2018 and 2019 than in 2020. Furthermore, the sensitivities of GeneXpert during 2018–2020 demonstrated a downward trend (80.9, 95% confidence intervals (CI) 76.8–85.0; 80.2, 95% CI 76.4–84.1 and 75.4, 95% CI 70.7–80.2, respectively). Approximately 69.0% (7557/10 946) of the TB cases with DST results were subjected to GeneXpert detection. Overall, the DR-TB status and the use of GeneXpert in Sichuan have improved, but DR-TB challenges remain. HIV testing for all TB cases is recommended.

The long-distance stable transport of relativistic electron beams (REBs) in plasmas is studied by full three-dimensional particle-in-cell simulations. Theoretical analysis shows that the beam transport is mainly influenced by three transverse instabilities, where the excitation of self-modulation instability, and the suppression of the filamentation instability and the hosing instability are important to realize the beam stable transport. By modulating the transport parameters such as the electron density ratio, the relativistic Lorentz factor, the beam envelopes and the density profiles, the relativistic bunches having a smooth density profile and a length of several plasma wave periods can suppress the beam-plasma instabilities and propagate in plasmas for long distances with small energy losses. The results provide a reference for the research of long-distance and stable transport of REBs, and would be helpful for new particle beam diagnosis technology and space active experiments.