Hand, foot and mouth disease (HFMD) is a common infection in the world, and its epidemics result in heavy disease burdens. Over the past decade, HFMD has been widespread among children in China, with Shanxi Province being a severely affected northern province. Located in the temperate monsoon climate, Shanxi has a GDP of over 2.5 trillion yuan. It is important to have a comprehensive understanding of the basic features of HFMD in those areas that have similar meteorological and economic backgrounds to northern China. We aimed to investigate epidemiological characteristics, identify spatial clusters and predict monthly incidence of HFMD. All reported HFMD cases were obtained from the Shanxi Center for Disease Control and Prevention. Overall HFMD incidence showed a significant downward trend from 2017 to 2020, increasing again in 2021. Children aged < 5 years were primarily affected, with a high incidence of HFMD in male patients (relative risk: 1.316). The distribution showed a seasonal trend, with major peaks in June and July and secondary peaks in October and November with the exception of 2020. Other enteroviruses were the predominant causative agents of HFMD in most years. Areas with large numbers of HFMD cases were primarily in central Shanxi, and spatial clusters in 2017 and 2018 showed a positive global spatial correlation. Local spatial autocorrelation analysis showed that hot spots and secondary hot spots were concentrated in Jinzhong and Yangquan in 2018. Based on monthly incidence from September 2021 to August 2022, the mean absolute error (MAE), mean absolute percentage error (MAPE), and root mean square error (RMSE) of the long short-term memory (LSTM) and seasonal autoregressive integrated moving average (SARIMA) models were 386.58 vs. 838.25, 2.25 vs. 3.08, and 461.96 vs. 963.13, respectively, indicating that the predictive accuracy of LSTM was better than that of SARIMA. The LSTM model may be useful in predicting monthly incidences of HFMD, which may provide early warnings of HFMD epidemics.

ABSTRACT IMPACT: Better understanding of the factors impacting disease severity and immunological response of MS patients on disease modifying therapy will enable better recommendations for vaccination options and risk mitigation strategies OBJECTIVES/GOALS: The Coronavirus Disease 2019 (COVID-19) and global health crisis has raised health concerns for patients with multiple sclerosis (MS). We aim to study the clinical characteristics, immunological laboratory data, and immunoglobulin response in patients with MS and COVID-19, to identify factors impacting disease severity and immune response. METHODS/STUDY POPULATION: Database search was done using DataDirect to search for MS patients who had tested positive for COVID-19 at the University of Michigan hospital. Patients with a positive nasopharyngeal swab polymerase chain reaction (PCR) for COVID-19 between March 1 and September 2020 were included. The primary outcome was the immunological laboratory data and immunoglobulin levels and the secondary outcome was their disease severity. We collected demographics, neurological history, MS treatment, Expanded Disability Scale Score (EDSS), comorbidities, and COVID-19 characteristics. A 7-point ordinal scale previously used to assess disease severity was used. Univariate and multivariate analyses will be performed to assess relationships between the collected variables. RESULTS/ANTICIPATED RESULTS: A total of 17 patients, mean age 53 (SD 11.6) years, mean disease duration, 6.2(SD 4.1) years were analyzed. 41% of patients had relapsing remitting multiple sclerosis, 17% had primary progressive MS. (88%) patients were on Disease Modifying Therapy (DMT) at the time of COVID-19 diagnosis. 2 patients died from COVID-19 complications. There was a higher proportion of patients with higher disease severity receiving Ocrelizumab. Only one patient showed positive IgG to SARS-CoV-2 after the resolution of infection. CBC with differential was obtained and a longitudinal follow-up of labs will be done. Regression analysis will be done to check the association between the use of DMT, immunological response, and COVID disease severity in them. The impact of COVID-19 on MS relapse, EDSS, and MRI activities will also be studied. DISCUSSION/SIGNIFICANCE OF FINDINGS: Recommendations to continue current DMT have been made, however, the immune response has not been correlated with the individual’s risk profile. Certain therapies may interfere with mounting a protective immune response of COVID-19 and this knowledge is crucial when advising patients regarding the choice of vaccine and risk mitigation strategies.

Post-testicular maturation of spermatozoa is crucial for attaining the morphological and functional capabilities needed for successful fertilization. Epididymal epithelia offer a favorable environment for spermatozoa that are stored long term in the turtle epididymis; however, sperm–epithelial interactions during storage, which are enormously important for sperm functional and morphological maturation, are still largely unknown in turtles. The present study examined the epididymis during the sperm-storage period (November–April) in the Chinese soft-shelled turtle (Pelodiscus sinensis). Light and transmission electron microscopy were used to determine the cellular features of each epididymal segment (caput, corpus, and cauda) and their epithelial interactions with the spermatozoa. Spermatozoa were mainly located in the lumena of caput, corpus, and cauda epididymides. Numerous spermatozoa were bound to apical surfaces of the epithelia, and several were even embedded in the epithelial cytoplasm of the caput and corpus epididymides. No embedded spermatozoa were found in the cauda epididymis. In all epididymal segments, principal and clear cells showed the synthetic activity, evidenced by a well-developed endoplasmic reticulum network and high and low electron-dense secretory materials, respectively. Principal and clear cells in the caput and corpus segments showed embedded spermatozoa in electron-dense secretions and in the lipid droplets within the cytoplasm. No lysosomes were observed around the embedded spermatozoa. The lumena of the caput and corpus segments showed few apocrine and low electron density secretions. In the lumen of the cauda epididymidis, different secretions, such as holocrine with low and high electron density and their fragmentation, apocrine, and dictyosome, were found and are summarized. Altogether, sperm physical interactions with secretions either in the cytoplasm of epithelium or in the lumen may support the viability, morphological maintenance, and transfer of various proteins involved in long-term sperm storage in the turtle. This interaction could help us to understand the mechanisms of long-term sperm storage and provide more insights into the reproductive strategies of turtle sperm preservation.

The seminiferous tubule (ST) is the location of spermatogenesis, where mature spermatozoa are produced with the assistance of Sertoli cells. The role of extracellular vesicles in the direct communication between Sertoli-germ cells in the ST is still not fully understood. In this study, we reported multivesicular bodies (MVBs) and their source of CD63-enriched exosomes by light and ultrastructure microscopy during the reproductive phases of turtles. Strong CD63 immunopositivity was detected at the basal region in the early and luminal regions of the ST during late spermatogenesis by immunohistochemistry (IHC), immunofluorescence (IF), and western blot (WB) analysis. Labeling of CD63 was detected in the Sertoli cell cytoplasmic processes that surround the developing germ cells during early spermatogenesis and in the lumen of the ST with elongated spermatids during late spermatogenesis. Furthermore, ultrastructure analysis confirmed the existence of numerous MVBs in the Sertoli cell prolongations that surround the round and primary spermatogonia during acrosome biogenesis and with the embedded heads of spermatids in the cytoplasm of Sertoli cells. Additionally, in spermatids, Chrysanthemum flower centers (CFCs) generated isolated membranes involved in MVBs and autophagosome formation, and their fusion to form amphiosomes was also observed. Additionally, autophagy inhibition by 3-methyladenine (after 24 h) increased CD63 protein signals during late spermatogenesis, as detected by IF and WB. Collectively, our study found MVBs and CD63 rich exosomes within the Sertoli cells and their response to autophagy inhibition in the ST during the spermatogenesis in the turtle.

The present study was designed to investigate the in vivo biological processes of multivesicular bodies (MVBs) and exosomes in mitochondria-rich cells (MRCs), goblet cells (GCs), and absorptive cells (ACs) in turtle intestines during hibernation. The exosome markers, cluster of differentiation 63 (CD63) and tumor susceptibility gene 101 (TSG101), were positively expressed in intestinal villi during turtle hibernation. The distribution and formation processes of MVBs and exosomes in turtle MRCs, GCs, and ACs were further confirmed by transmission electron microscopy. During hibernation, abundantly secreted early endosomes (ees) were localized in the luminal and basal cytoplasm of the MRCs and ACs, and late endosomes (les) were dispersed with the supranuclear parts of the MRCs and ACs. Many “heterogeneous” MVBs were identified throughout the cytoplasm of the MRCs and ACs. Interestingly, the ees, les, and MVBs were detected in the cytoplasm of the GCs during hibernation; however, they were absent during nonhibernation. Furthermore, the exocytosis pathways of exosomes and autophagic vacuoles were observed in the MRCs, GCs, and ACs during hibernation. In addition, the number of different MVBs with intraluminal vesicles (ILVs) and heterogeneous endosome–MVB–exosome complexes was significantly increased in the MRCs, GCs, and ACs during hibernation. All these findings indicate that intestinal epithelial cells potentially perform a role in the secretion of MVBs and exosomes, which are essential for mucosal immunity, during hibernation.

Maternal high-fat diet (HFD) alters hypothalamic programming and disrupts offspring energy homeostasis in rodents. We previously reported that the loss of ERα signaling partially blocks the effects of maternal HFD in female offspring fed a standard chow diet. In a companion study, we determined if the effects of maternal HFD were magnified by an adult obesogenic diet in our transgenic mouse models. Heterozygous ERα knockout (wild-type (WT)/KO) dams were fed a control breeder chow diet (25% fat) or a semipurified HFD (45% fat) 4 weeks prior to mating with heterozygous males (WT/KO or WT/ knockin) to produce WT, ERα KO, or ERα knockin/knockout (KIKO) (no estrogen response element (ERE) binding) female offspring, which were fed HFD for 20 weeks. Maternal HFD potentiated the effects of adult HFD on KIKO and KO body weight due to increased adiposity and decreased activity. Maternal HFD also produced KIKO females that exhibit KO-like insulin intolerance and impaired glucose homeostasis. Maternal HFD increased plasma interleukin 6 and monocyte chemoattractant protein 1 levels and G6pc and Pepck liver expression only in WT mice. Insulin and tumor necrosis factor α levels were higher in KO offspring from HFD-fed dams. Arcuate and liver expression of Esr1 was altered in KIKO and WT, respectively. These data suggest that loss of ERE-dependent ERα signaling, and not total ERα signaling, sensitizes females to the deleterious influence of maternal HFD on offspring energy and glucose potentially through the control of peripheral inflammation and hypothalamic and liver gene expression. Future studies will interrogate the tissue-specific mechanisms of maternal HFD programming through ERα signaling.

The Early Palaeozoic geology of the South China Craton (SCC) is characterized by an Early Palaeozoic intracontinental orogen with folded pre-Devonian strata and migmatites, MP/MT metamorphic rocks and Silurian post-orogenic peraluminous magmatic rocks in both the Yangtze and the Cathaysia blocks. In this contribution, we present new zircon U–Pb ages and Hf isotope data for detrital zircons from the Neoproterozoic to Silurian sedimentary sequences in the southeastern Yangtze Block. Samples from Neoproterozoic rocks generally display a major peak at 900–560 Ma, whereas samples from Lower Palaeozoic rocks are characterized by several broader peaks within the age ranges 600–410 Ma, 1100–780 Ma, 1.6–1.2 Ga and 2.8–2.5 Ga. Provenance analysis indicates that the 900–630 Ma detritus in Cryogenian to Ediacaran samples was derived from the Late Neoproterozoic igneous rocks in South China that acted as an internal source. The occurrence of 620–560 Ma detritus indicates the SE Yangtze was associated with Late Neoproterozoic arc volcanism along the north margin of East Gondwana. The change of provenance resulted in the deposition of 550–520 Ma and 1.1–0.9 Ga detrital zircons in the Cambrian–Ordovician sedimentary rocks. The εHf(t) values of these detrital zircons are similar to those of zircons from NW Australia–Antarctica and South India. This change of provenance in the Cambrian can be attributed to the intracontinental subduction between South China and South Qiangtang, and the convergence of India and Australia when East Gondwana finally amalgamated.

Detrital zircons are often used to constrain the maximum sedimentary age of strata and sedimentary provenance. This study aimed at reconstructing the Cryogenian palaeogeography of the Yangtze Domain based on U–Pb ages and Lu–Hf isotopic signatures of detrital zircons from sandstones in the southeastern part of the Yangtze Domain. U–Pb ages of the youngest detrital zircon grains from the Niuguping, Gucheng and Datangpo formations yielded average ages of 712±24 Ma, 679.2±6.2 Ma and 665.1±7.4 Ma, respectively, which are close to the depositional ages of their respective formations. An integrated study of detrital zircon Lu–Hf isotopes and U–Pb ages from three samples revealed six main peak ages in the samples from the Anhua section at c. 680 Ma, c. 780 Ma, c. 820 Ma, c. 940 Ma, c. 2000 Ma and c. 2500 Ma. The characteristics of the U–Pb ages and Hf isotopes indicate a link between the north and southeast margins of the Yangtze Domain as early as c. 680 Ma, and the provenance of the coeval sedimentary sequences in the SE Yangtze Domain was the South Qinling Block on the northern margin of the Yangtze Domain. The provenance analysis on the c. 680 Ma detritus composing upper Neoproterozoic strata in the Yangtze Domain revealed that the detritus was transported southward from South Qinling to the southeast margin of the Yangtze Domain through the Exi Strait, but was hindered by the Jiangnan Orogenic Belt.

In this study, the cross-section of electron-selective titanium oxide (TiO2) contacts for n-type crystalline silicon solar cells were investigated by transmission electron microscopy. It was revealed that the excellent cell efficiency of 21.6% obtained on n-type cells, featuring SiO2/TiO2/Al rear contacts and after forming gas annealing (FGA) at 350°C, is due to strong surface passivation of SiO2/TiO2 stack as well as low contact resistivity at the Si/SiO2/TiO2 heterojunction. This can be attributed to the transformation of amorphous TiO2 to a conducting TiO2−x phase. Conversely, the low efficiency (9.8%) obtained on cells featuring an a-Si:H/TiO2/Al rear contact is due to severe degradation of passivation of the a-Si:H upon FGA.

Nanogenerators (NGs) have great potential to solve the problems of energy depletion and environmental pollution. Here, two types of flexible nanogenerators (FNGs) based on graphene oxide (GO) and multiwall carbon nanotubes (MW-CNTs) are presented. The peak output voltage and current of GO based FNG reached up to 2 V and 30 nA, respectively, under 15 N force at 1 Hz. Moreover, the output voltage could be improved to 34.4 V when the frequency was increased to 10 Hz. It was also found the output voltage increased from 0.1 V to 2.0 V using a released GO structure. The other FNG was made by MW-CNTs mixed with ZnO nanoparticles (NPs). Its output voltage and power reached up to 7.5 V and 18.75 mW, respectively, which is much larger than that of bare ZnO based FNG. Furthermore, a peak voltage of 30 V could be gained by stamping one’s foot on the FNG. Finally, a modified NG was fabricated using four springs and two flexible layers. As a result, the voltage and power reached up to 9 V and 27mW, respectively. These works may bring out broad applications in energy harvesting.

This paper reports low temperature, digital control, fast synthesis of high-quality boron nitride nanosheets (BNNSs) and their electronic device application. Raman scattering spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM) are used to characterize the BNNSs. With the synthesized various BNNSs, two prototypic types of deep UV photodetectors have been fabricated, and sensitivity, response and recovery times, as well as repeatability have been characterized. Effects of period and thickness of BNNSs on the properties of prototypic photodetectors are also discussed.