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Abstract Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC‐1 study. Cytokines, especially interleukin (IL)‐6, are known suppressors of cytochrome P450 (CYP) enzymes' activity. A physiologically based pharmacokinetic model evaluated the impact of IL‐6 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5). Two IL‐6 kinetics profiles were assessed, the mean IL‐6 profile with a maximum concentration (Cmax) of IL‐6 (21 pg/mL) and the IL‐6 profile of the patient presenting the highest IL‐6 Cmax (288 pg/mL) among patients receiving the recommended phase II dose of teclistamab in MajesTEC‐1. For the mean IL‐6 kinetics profile, teclistamab was predicted to result in a limited change in exposure of CYP substrates (area under the curve [AUC] mean ratio 0.87–1.20). For the maximum IL‐6 kinetics profile, the impact on omeprazole, simvastatin, midazolam, and cyclosporine exposure was weak to moderate (mean AUC ratios 1.90–2.23), and minimal for caffeine and s‐warfarin (mean AUC ratios 0.82–1.25). Maximum change in exposure for these substrates occurred 3–4 days after step‐up dosing in cycle 1. These results suggest that after cycle 1, drug interaction from IL‐6 effect has no meaningful impact on CYP activities, with minimal or moderate impact on CYP substrates. The highest risk of drug interaction is expected to occur during step‐up dosing up to 7 days after the first treatment dose (1.5 mg/kg subcutaneously) and during and after CRS.

Trimethylamine oxide (TMAO) is a microbiota-derived metabolite, and numerous studies have shown that it could regulate fat metabolism in humans and mice. However, few studies have focused on the effects of TMAO on fat deposition in growing-finishing pigs. This study aimed to investigate the effect of TMAO on fat deposition and intestinal microbiota in growing-finishing pigs. Sixteen growing pigs were randomly divided into 2 groups and fed with a basal diet with 0 or 1 g/kg TMAO for 149 d. The intestinal microbial profiles, fat deposition indexes, and fatty acid profiles were measured. These results showed that TMAO supplementation had a tendency to decrease lean body mass (P

Radiofrequency ablation (RFA) is an effective treatment for hepatocellular carcinoma (HCC), but the recurrence rate remains high due to angiogenesis in residual cancer cells. We used thermal stimulation to simulate the post-RFA microenvironment. The expression profile of circRNAs between normal control HCC cell-derived exosomes and exosomes after heat stimulation were analyzed by RNA sequencing. Quantitative real-time PCR was applied to evaluate the expression of circPTPRK in exosomes and human umbilical vein endothelial cells (HUVECs). Then, the functions of heat-stimulated HCC cell-derived exosomes and exosomal circPTPRK on HUVECs were unveiled. Transcriptome sequencing was utilized to determine targeted genes of circPTPRK. Heat-stimulated HCC cell-derived exosomes augmented cell proliferation, migration, and angiogenesis of HUVECs. In total, 229 differentially expressed circRNAs were obtained, including 211 upregulated circRNAs and 18 downregulated circRNAs in heat-stimulated HCC cell-derived exosomes. The expression of circPTPRK was remarkably increased in heat-stimulated HCC cell-derived exosomes and the HUVECs incubated with them. Heat-stimulated HCC cell-derived exosomes with circPTPRK knockdown significantly inhibited cell proliferation, migration, and angiogenesis of HUVECs. Mechanistic studies indicated that PLA2G4E is a downstream target of circPTPRK, and PLA2G4E overexpression reversed the inhibitory effect of circPTPRK knockdown on HUVEC angiogenesis. Our results indicated that exosomal circPTPRK activated HUVEC angiogenesis by upregulating PLA2G4E expression.

The largemouth bass is a native species of North America that was first introduced to mainland China in the 1980s. In recent years, it has been extensively farmed in China due to its high meat quality and broad adaptability. In this study, we collected growth trait data from 1,066 largemouth bass individuals across two populations. We generated an average of approximately 7× sequencing coverage for these fish using Illumina sequencers. From the samples, we identified 2,695,687 SNPs and retained 1,809,116 SNPs for further analysis after filtering. To estimate the number of genome-wide effective SNPs, we performed LD pruning with PLINK software and identified 77,935 SNPs. Our GWAS revealed 15 SNPs associated with six growth traits. We identified a total of 24 genes related to growth, with three genes—igf1, myf5, and myf6—directly associated with skeletal muscle development and growth, located near the leading SNP on chromosome 23. Other candidate genes are involved in the development of tissues and organs or other physiological processes. These findings provide a valuable set of SNPs and genes that could be useful for genetic breeding programs aimed at enhancing growth in largemouth bass.

PurposeTo compare the long-term efficacy of the parallel stent graft (PSG), fenestrated stent graft (FSG), and branched stent graft (BSG) techniques to treat thoracoabdominal aortic pathologies.Materials and methodsIn total, 291 patients with thoracic aortic aneurysm (TAA) and dissection (TAD) involving visceral arteries who underwent PSG (n = 85; 15 TAA and 70 TAD), FSG (n = 107; 47 TAD and 60 TAA), or BSG (n = 99; 37 TAD and 62 TAA) were included from multiple centers from January 2015 to December 2022, and a total of 1,108 visceral aortic branches were reconstructed.ResultsThe average reconstruction time of each visceral aortic branch for FSG, BSG, and PSG is 27.5 ± 12.1, 23.2 ± 11.9, and 18.8 ± 11.8 min, respectively (P

Background: Although studies in China have found that school bullying is prevalent among adolescents, most relevant research has focused on southern China, while research in northern China is limited. This study aimed to explore ethnic disparities in the socio-demographic determinants of school bullying in Inner Mongolia, a northern region of China. Methods: A cross-sectional study was conducted among 2891 adolescents in Inner Mongolia, China, from September to December 2022. Data on participants' sociodemographic characteristics and school bullying experiences were collected through questionnaires. Multivariate logistic regression analyses, stratified by ethnicity, were employed to examine factors associated with school bullying. Furthermore, subgroup analyses and interaction tests were conducted to explore potential effect modifiers of the relationship between ethnicity and bullying. Results: The prevalence of school bullying was 18.99 % (549/2891) overall, with 17.96 % (420/2339) among Han and 23.37 % (129/552) among ethnic minorities. Minority adolescents faced a higher risk of bullying compared to Han (OR = 1.35, 95 % CI: 1.08–1.69, P 0.05). Limitations: This cross-sectional study has limitations in establishing causal relationships between identified associated factors and school bullying. Conclusions: Ethnic minority adolescents in Inner Mongolia, China, especially middle school students, face a higher risk of school bullying than their Han peers. The differential impact of maternal education, family economic status, and family structure on bullying risk between Han and minority adolescents underscores the need for culturally sensitive, targeted interventions that consider the unique challenges faced by ethnic minority students.

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) μg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial–mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

ObjectiveThis paper focuses on using reinforcement learning-based automatic generation technology to generate loading and unloading schemes for the liquid cargo tanks of oil tankers. MethodsUsing the cargo capacity of an actual operating oil tanker as the input and the loading rates of the cargo tank and ballast water tank as the targets, an intelligent agent and environment are built based on Unity ML-Agents. The agent is trained using the PyTorch framework, and a reward function calculation method that comprehensively considers the loading time and changes in the trim amplitude is proposed. Finally, example analysis is carried out to validate the feasibility of the proposed method. ResultsThe results show that the trained agent can learn effective strategies for achieving the autonomous generation of liquid cargo tank loading schemes. ConclusionsThis study proves that it is reasonable and feasible to apply reinforcement learning to solve the problem of the autonomous generation of liquid cargo tank loading schemes under multi-objective conditions.

Abstract Objective To improve the PET image quality by a deep progressive learning (DPL) reconstruction algorithm and evaluate the DPL performance in lesion quantification. Methods We reconstructed PET images from 48 oncological patients using ordered subset expectation maximization (OSEM) and deep progressive learning (DPL) methods. The patients were enrolled into three overlapped studies: 11 patients for image quality assessment (study 1), 34 patients for sub-centimeter lesion quantification (study 2), and 28 patients for imaging of overweight or obese individuals (study 3). In study 1, we evaluated the image quality visually based on four criteria: overall score, image sharpness, image noise, and diagnostic confidence. We also measured the image quality quantitatively using the signal-to-background ratio (SBR), signal-to-noise ratio (SNR), contrast-to-background ratio (CBR), and contrast-to-noise ratio (CNR). To evaluate the performance of the DPL algorithm in quantifying lesions, we compared the maximum standardized uptake values (SUVmax), SBR, CBR, SNR and CNR of 63 sub-centimeter lesions in study 2 and 44 lesions in study 3. Results DPL produced better PET image quality than OSEM did based on the visual evaluation methods when the acquisition time was 0.5, 1.0 and 1.5 min/bed. However, no discernible differences were found between the two methods when the acquisition time was 2.0, 2.5 and 3.0 min/bed. Quantitative results showed that DPL had significantly higher values of SBR, CBR, SNR, and CNR than OSEM did for each acquisition time. For sub-centimeter lesion quantification, the SUVmax, SBR, CBR, SNR, and CNR of DPL were significantly enhanced, compared with OSEM. Similarly, for lesion quantification in overweight and obese patients, DPL significantly increased these parameters compared with OSEM. Conclusion The DPL algorithm dramatically enhanced the quality of PET images and enabled more accurate quantification of sub-centimeters lesions in patients and lesions in overweight or obese patients. This is particularly beneficial for overweight or obese patients who usually have lower image quality due to the increased attenuation.

Primary pontine hemorrhage (PPH) is a particularly grave form of hemorrhagic stroke, characterized by its significant mortality rate. stereotactic hematoma puncture and drainage is a procedure that has been shown to improve the prognosis of patients with PPH. However, there are currently no established criteria for selecting patients for this procedure. We contrasted the clinical outcomes of PPH patients treated with stereotactic hematoma puncture and drainage with those who received conservative treatment in this study. We conducted logistic regression analysis to identify the risk factors associated with postoperative mortality. A mortality risk nomogram was then constructed using these risk factors. A total of 127 conservatively treated patients and 96 patients who underwent stereotactic hematoma puncture and drainage were included in this study. In the surgical group, the 30-day mortality rate stood at 28.1%, significantly lower than the 43.3% observed in the control group (p = 0.02). Age, along with the Glasgow Coma Scale (GCS) score and hematoma size, were identified as independent risk factors associated with death within 30 days post-surgery. The mortality risk nomogram was well calibrated and discriminatory, with a c-index of 0.878 (95% CI 0.80–0.95) as validated by bootstrapping, and a c-index of 0.849. This study provides a predictive model for selecting patients who are most likely to benefit from stereotactic hematoma puncture and drainage. The results of this study could be helpful to neurosurgeons in their decision-making process. However, further external validation is necessary to confirm these findings.

Abstract Background For patients with varicose veins, the goal is to relieve pain and swelling, reduce the severity of edema, improve skin changes, and heal ulcers associated with venous disease. Compression therapy is the cornerstone of their management. Several studies have shown that wearing an elastic bandage for the first 24 h and then a compression stocking for a week can effectively reduce the pain after thermal ablation. However, in clinical practice, patient compliance with this treatment could be better, considering difficulties in pulling up and removing the compression stocking, tightness, and skin irritation because these must be worn for a prolonged period. A potential solution to battling these barriers is short-term compression therapy. Besides, the effect and necessity of wearing compression stockings after thermal ablation have been questioned. Based on current clinical experience and limited evidence, although some scholars have suggested that compression therapy may be an unnecessary adjunctive therapy after thermal ablation, there is still a great deal of uncertainty in the absence of compression therapy after thermal ablation compared to compression therapy. Therefore, we advocate further research to evaluate the clinical effect of short-term postoperative compression therapy. Furthermore, well-designed randomized controlled trials are needed. Methods A prospective, multicenter, non-inferiority randomized controlled trial is designed to evaluate the non-inferiority of target vein occlusion rate at 3 months. Three hundred and sixty patients will be randomly assigned in a 1:1 ratio to one of the following treatments: (A) 3 M™ Coban™ elastic bandage for 48 h or (B) 3 M™ Coban™ elastic bandage for the first 24 h and then a class II compression full-length stocking (23–32 mm Hg) for 1 week. The two groups will be compared on several variables, including target vein occlusion rate at 3 months (primary outcome indicator), pain, quality of life, clinical severity of varicose veins, postoperative complications, time to return to regular work, and compliance. Discussion Suppose the effect of the 3 M™ Coban™ elastic bandage for 48 h proves to be non-inferior to long-term compression therapy. In that case, this short-term treatment may contribute to a future update of clinical guidelines for compression therapy after thermal ablation of varicose veins, resulting in higher patient compliance and better postoperative quality of life. Trial registration Clinical Trials NCT05840991 . Registered on May 2023.

Abstract A solar neutrino detector relying on the charged-current (CC) interaction of $$\nu _e$$ ν e on $$\mathrm{{}^{7}Li}$$ 7 Li is attractive. The total CC interaction cross-section weighted by the solar $$^8$$ 8 B electron neutrino spectrum is approximately 60 times that of the neutrino-electron elastic scattering process. The final state effective kinetic energy after the CC interaction on $$\mathrm{{}^{7}Li}$$ 7 Li directly reflects the neutrino energy, which stands in sharp contrast to the plateau structure of recoil electrons of the elastic scattering. The recent measurement of the optical properties of saturated LiCl water solution, especially the long attenuation length, has once again aroused our interest in LiCl. In this work, with new B(GT) experimental measurements, the CC cross-section on $$\mathrm{{}^{7}Li}$$ 7 Li is reevaluated to be $$3.759\times 10^{-42}~\textrm{cm}^2$$ 3.759 × 10 - 42 cm 2 . Given the high solubility of LiCl of 74.5 g/100 g water at 10 $$^\circ $$ ∘ C and the high natural abundance of 92.41% of $$\mathrm{{}^{7}Li}$$ 7 Li , a solar neutrino detection proposal is made. The detector with high concentration LiCl water solution has a comparable CC event rate of $$\nu _e$$ ν e on $$\mathrm{{}^{7}Li}$$ 7 Li with that of neutrino-electron elastic scattering. The contained $$\mathrm{{}^{35}Cl}$$ 35 Cl , $$\mathrm{{}^{6}Li}$$ 6 Li , and H also make a delayed-coincidence detection for $${{\bar{\nu }}}_e$$ ν ¯ e possible. The advantages of studying the upturn effect of solar neutrino oscillation, light sterile neutrinos, and Earth matter effect are investigated in detail. The sensitivities in discovering solar neutrino upturn and light sterile neutrinos are presented.

To investigate difference in the quality of the different parts (back, tail muscles, and fish skin) of Opsariichthys bidens from pond and rice field cultures, a comparative study was conducted in terms of nutritional composition, volatile flavor profiles and gut microbiota. In detail, the texture, free amino acids, fatty acids were further assessed. The results suggested that the moisture content, crude protein and crude fat content in the skin of O. bidens are higher than those in the back and tail muscles, regardless of breeding modes. The fish cultured in the rice field had a higher protein content than those from the pond culture, while the fat content of the rice field-cultured fish was significantly low compared to the fish from the pond culture, especially in the back and tail parts. A total of 43 volatile components were detected by Gas Chromatography–Mass Spectrometry (GC-MS), with a maximum of 18 types of aldehydes and the highest concentration being nonanal. Compared to pond cultures, the fish from the rice field cultures showed more abundant flavor composition and odor-active compounds. The total content of DHA (Docosahexaenoic Acid) and EPA (Eicosapentaenoic Acid) in the rice field-cultured fish was higher than that of the pond group, while no significant disparity in amino acid composition was observed (p > 0.05). Comparative and clustering analyses of gut microbiota revealed notable discrepancies in the gut microbiota of O. bidens from two aquaculture systems. However, an inherent correlation between the gut microbiome and meat quality would be further emphasized in further studies. This study can offer a theoretical reference for the development of high-quality aquatic products by selecting the appropriate aquaculture models.

Abstract Congenital anomalies of the kidney and urinary tract (CAKUT) are disorders resulting from defects in the development of the kidneys and their outflow tract. Copy number variations (CNVs) have been identified as important genetic variations leading to CAKUT, whereas most CAKUT-associated CNVs cannot be attributed to a specific pathogenic gene. Here we construct coexpression networks involving long noncoding RNAs (lncRNAs) within these CNVs (CNV-lncRNAs) using human kidney developmental transcriptomic data. The results show that CNV-lncRNAs encompassed in recurrent CAKUT associated CNVs have highly correlated expression with CAKUT genes in the developing kidneys. The regulatory effects of two hub CNV-lncRNAs (HSALNG0134318 in 22q11.2 and HSALNG0115943 in 17q12) in the module most significantly enriched in known CAKUT genes (CAKUT_sig1, P = 1.150 × 10−6) are validated experimentally. Our results indicate that the reduction of CNV-lncRNAs can downregulate CAKUT genes as predicted by our computational analyses. Furthermore, knockdown of HSALNG0134318 would downregulate HSALNG0115943 and affect kidney development related pathways. The results also indicate that the CAKUT_sig1 module has function significance involving multi-organ development. Overall, our findings suggest that CNV-lncRNAs play roles in regulating CAKUT genes, and the etiologies of CAKUT-associated CNVs should take account of effects on the noncoding genome.

Phosphatidylethanolamine (PE), a multifunctional phospholipid, is necessary for neonate development. This study aimed to explore the impact of the regulation of exogenous PE on postnatal growth retardation (PGR) by improving intestinal barrier function. Thirty-two neonatal pigs were divided into four groups according to their body weight (BW 2.79 ± 0.50 kg or 1.88 ± 0.40 kg) at 7 days old, CON-NBW, PE-NBW, CON-PGR, and PE-PGR. PE was supplemented to NBW piglets and PGR piglets during lactation and post-weaning periods. Compared with the NBW piglets, the growth performance of PGR piglets was lower, while PE improved the poor growth performance. PGR piglets showed injured intestinal morphology, as evidenced by the reduced ratio of villus height to crypt depth (VH/CD) and goblet cell numbers in the jejunum and ileum. PE recovered the intestinal barrier injury by increasing VH/CD and goblet cell numbers. The decreased MUC2 mRNA and protein expressions were observed in the small intestine of PGR piglets, and PE remarkably increased the expression of MUC2. Mechanistically, PE increased the goblet cell differentiation promoting gene spdef mRNA levels and reduced the mRNA expressions involved in endoplasmic reticulum stress in the jejunal and ileal mucosa of PGR piglets. Overall, we found that PE alleviated growth retardation by regulating intestinal health and generalized its application in neonates.

Abnormal hepatic energy metabolism limits the growth and development of piglets. We hypothesized that β-hydroxybutyrate (BHB) might improve the growth performance of piglets by maintaining hepatic caloric homeostasis. A total of 30 litters of newborn piglets were tracked, and 30 postnatal growth retardation (PGR) piglets and 40 healthy piglets were selected to treat with normal saline with or without BHB (25 mg/kg/days) at 7-d-old. At the age of 42 days, 8 piglets in each group were sacrificed, and serum and liver were collected. Compared with the healthy-control group piglets, PGR piglets showed lower body weight (BW) and liver weight (p

Obstructive sleep apnea (OSA) and central sleep apnea (CSA) are two main types of sleep disordered breathing (SDB). While the changes in cerebral hemodynamics triggered by OSA events have been well studied using near-infrared spectroscopy (NIRS), they are essentially unknown in CSA in adults. Therefore, in this study, we compared the changes in cerebral oxygenation between OSA and CSA events in adult patients using NIRS. Cerebral tissue oxygen saturation (StO2) in 13 severe SDB patients who had both CSA and OSA events was measured using frequency-domain NIRS. The changes in cerebral StO2 desaturation and blood volume (BV) in the first hour of natural sleep were compared between different types of respiratory events (i.e., 277 sleep hypopneas, 161 OSAs and 113 CSAs) with linear mixed-effect models controlling for confounders. All respiratory events occurred during non-rapid eye movement (NREM) sleep. We found that apnea events induced greater cerebral desaturations and BV fluctuations compared to hypopneas, but there was no difference between OSA and CSA. These results suggest that cerebral autoregulation in our patients are still capable to counteract the pathomechanisms of apneas, in particularly the negative intrathoracic pressure (ITP) caused by OSA events. Otherwise larger BV fluctuations in OSA compared to CSA should be observed due to the negative ITP that reduces cardiac stroke volume and leads to lower systematic blood supply. Our study suggests that OSA and CSA may have similar impact on cerebral oxygenation during NREM sleep in adult patients with SDB.

Abstract Hematogenous metastasis is the main approach for colorectal cancer liver metastasis (CRCLM). However, as the gatekeepers in the tumor vessels, the role of TPCs in hematogenous metastasis remains largely unknown, which may be attributed to the lack of specific biomarkers for TPC isolation. Here, microdissection combined with a pericyte medium‐based approach is developed to obtain TPCs from CRC patients. Proteomic analysis reveals that TRP channel‐associated factor 2 (TCAF2), a partner protein of the transient receptor potential cation channel subfamily M member 8 (TRPM8), is overexpressed in TPCs from patients with CRCLM. TCAF2 in TPCs is correlated with liver metastasis, short overall survival, and disease‐free survival in CRC patients. Gain‐ and loss‐of‐function experiments validate that TCAF2 in TPCs promotes tumor cell motility, epithelial‐mesenchymal transition (EMT), and CRCLM, which is attenuated in pericyte‐conditional Tcaf2‐knockout mice. Mechanistically, TCAF2 inhibits the expression and activity of TRPM8, leading to Wnt5a secretion in TPCs, which facilitates EMT via the activation of the STAT3 signaling pathway in tumor cells. Menthol, a TRPM8 agonist, significantly suppresses Wnt5a secretion in TPCs and CRCLM. This study reveals the previously unidentified pro‐metastatic effects of TPCs from the perspective of cold‐sensory receptors, providing a promising diagnostic biomarker and therapeutic target for CRCLM.

Chito-oligosaccharides (COS) and β-glucan are gradually being applied in aquaculture as antioxidants and immunomodulators. However, this study examined the effects of dietary supplementation of COS and β-glucan on the water quality, gut microbiota, intestinal morphology, non-specific immunity, and meat quality of Chinese soft-shell turtle. To investigate the possible mechanisms, 3-year-old turtles were fed basal diet (CK group) and 0.1%, 0.5%, and 1% COS or β-glucan supplemented diet for 4 weeks. Colon, liver, blood and muscle tissues, colon contents, water and sediment of paddy field samples were collected and analyzed after feeding 2 and 4 weeks. The results indicated that COS and β-glucan altered microbial community composition and diversity in Chinese soft-shell turtles. The relative abundance of Cellulosilyticum, Helicobacter and Solibacillus were increased after feeding COS, while Romboutsia, Akkermansia and Paraclostridium were increased after feeding β-glucan, whereas Cetobacterium, Vibrio and Edwardsiella were enriched in the control group. Furthermore, colon morphology analysis revealed that COS and β-glucan improved the length and number of intestinal villi, and the effect of 0.5% β-glucan was more obvious. Both β-glucan and COS significantly improved liver and serum lysozyme activity and antibacterial capacity. COS significantly increased the total antioxidant capacity in the liver. Further, 0.1% β-glucan significantly increased the activity of hepatic alkaline phosphatase, which closely related to the bacteria involved in lipid metabolism. Moreover, dietary supplementation with 1% COS and 1% β-glucan significantly enhanced the content of total amino acids, especially umami amino acids, in muscle tissue, with β-glucan exerting a stronger effect than COS. Additionally, these two prebiotics promoted the quality of culture water in paddy fields and reshaped the bacterial community composition of aquaculture environment. All these phenotypic changes were closely associated with the gut microbes regulated by these two prebiotics. In summary, the findings suggest that dietary supplementation with COS and β-glucan in Pelodiscus sinensis could modulate the gut microbiota, improve intestinal morphology, enhance non-specific immunity and antioxidant capacity of liver and serum, increase meat quality, and improve the culture water environment. This study provides new insights and a comprehensive understanding of the positive effects of COS and β-glucan on Pelodiscus sinensis.

Enterotoxigenic Escherichia coli (ETEC) is a common diarrheal pathogen in humans and animals. To prevent and treat ETEC induced diarrhea, we synthesized mannan oligosaccharide selenium (MOSS) and studied its beneficial effect on ETEC-induced diarrhea. A total of 32 healthy weaned piglets (6.69 ± 0.01 kg) were randomly divided into four groups: NC group (Basal diet), MOSS group (0.4 mg/kg MOSS supplemented diet), MOET group (0.4 mg/kg MOSS supplemented diet + ETEC treatment), ETEC group (ETEC treatment). NC and ETEC group fed with basal diet, MOSS and MOET group fed with the MOSS supplemented diet. On the 8th and 15th day of the experiment, MOET and ETEC group were gavaged with ETEC, and NC and MOSS group were gavaged with stroke-physiological saline solution. Our data showed that dietary MOSS supplementation increased average daily gain (ADG) and average daily feed intake (ADFI) and significantly decreased diarrhea index and frequency in ETEC-treated piglets. MOSS did not affect the α diversity and β diversity of ileal microbial community, but it significantly decreased the proportion of lipopolysaccharide biosynthesis in ileal microbial community. MOSS supplementation regulated colonic microbiota community composition, which significantly increased carbohydrate metabolism, and inhibited lipopolysaccharide biosynthesis pathway in colonic microbial community. Moreover, MOSS significantly decreased inflammatory stress, and oxidative stress in ETEC treated piglets. Furthermore, dietary MOSS supplementation significantly decreased intestinal barrier permeability, and alleviated ETEC induced intestinal mucosa barrier irritation. In conclusion, our study showed that dietary MOSS supplementation ameliorated intestinal mucosa barrier, and regulated intestinal microbiota to prevent ETEC induced diarrhea in weaned piglets.

A transcriptomic analysis of lncRNAs within copy-number variations identifies HSALNG0104472 as a potential lncRNA effector of cardiac defects in non-syndromic congenital heart disease.

ObjectiveCargo loading and unloading plan generation time and safety evaluation have a great influence on the handling efficiency. To this end, this paper introduce weight coefficient searching genetic algorithm into the plan generation. MethodsLoading safety status mainly involves draft limitation, intact stability checking, hyrostatic strength checking and compatibility between the generated loading and unloading plan and preset process. In this study, a non-deterministic polynomial and corresponding optimization objective functions are established to solve the loading and unloading scheme generation problem of liquid cargo carriers. The weight of each influence factor in the objective function is changed and recorded in sequence to form an optimal objective function cluster. The optimal solution of each member in the cluster is then carried out through an elitist preservation genetic algorithm in order to provide an optimal solution set. On this basis, a comparison is made with the loading and unloading plan of a very large crude oil carrier (VLCC) generated by the linear fitting methodResultsThe ship draft status is more consistent with the target, and the stability state is obviously better than that of the user preset plan in each loading/unloading step generated by this algorithm. ConclusionThe weight coefficient searching genetic algorithm based on elitist preservation proposed in this paper can improve the accuracy and reliability of the liquid cargo carrier loading sequence.

Abstract Main goal of the JUNO experiment is to determine the neutrino mass ordering using a 20 kt liquid-scintillator detector. Its key feature is an excellent energy resolution of at least 3% at 1 MeV, for which its instruments need to meet a certain quality and thus have to be fully characterized. More than 20,000 20-inch PMTs have been received and assessed by JUNO after a detailed testing program which began in 2017 and elapsed for about four years. Based on this mass characterization and a set of specific requirements, a good quality of all accepted PMTs could be ascertained. This paper presents the performed testing procedure with the designed testing systems as well as the statistical characteristics of all 20-inch PMTs intended to be used in the JUNO experiment, covering more than fifteen performance parameters including the photocathode uniformity. This constitutes the largest sample of 20-inch PMTs ever produced and studied in detail to date, i.e. 15,000 of the newly developed 20-inch MCP-PMTs from Northern Night Vision Technology Co. (NNVT) and 5000 of dynode PMTs from Hamamatsu Photonics K. K.(HPK).

Reportedly, proteins involved in lipid metabolism change significantly in the jejunal crypt cells of early-weaned piglets, but the exact lipid profile change remains uncertain. In the present study, 32 piglets weaned at 21 d of age were randomly divided into 4 groups with 8 replicates. The jejunal crypt cells of a group of piglets on the post-weaning day (PWD) 1, 3, 7, and 14 were isolated per time point. Crypt cell lipid profiles were analyzed using ultra-high-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry. This study showed that piglets suffered the greatest weaning stress on PWD 3 in terms of the lowest relative weight of the small intestine, the highest relative weight of the spleen, and the highest levels of malondialdehyde, cholesterol, and low-density lipoprotein cholesterol. The lipid profile of jejunal crypt cells including carnitine, sulfatide, sphingomyelin, hexosylceramide, and ceramide greatly changed after weaning, especially between PWD 3 and 14 (P

With the increasing demand for high-quality pork, more nutritional substances have been studied for the regulation of meat quality. Zero-dimensional fullerenes (C60) can modulate the biological behavior of a variety of cell lines and animals. In this study, we report the biological effects of C60 on finishing pigs at different concentrations. A total of 24 barrows (Duroc × Large White × Landrace), with an average body weight of 21.01 ± 0.98 kg, were divided into 3 groups and each treated daily with C60 (100 or 200 mg per kg feed) or a control diet until the end of the experiment. Our results showed that dietary C60 supplementation improved flesh color, marbling scores, and flavor amino acid contents of longissimus dorsi (LD) of growing-finishing pigs (P

Aspartate (asp), glutamate (glu), and glutamine (gln) are the major energy fuels for the small intestine, and it had been indicated in our previous study that the mix of these three amino acid supplementations could maintain intestinal energy homeostasis. This study aimed to further investigate whether the treatment of gln, glu, and asp in low energy diet affects the intestinal barrier integrity and amino acid pool in weaning piglets. A total of 198 weaned piglets were assigned to 3 treatments: control (basal diet + 1.59% L-Ala); T1 (basal diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp); and T2 (low energy diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp). The blood, jejunum, and ileum were obtained on day 5 or on day 21 post-weaning, respectively. Our results showed that T1 and T2 treatments increased the abundances of occludin, claudin-1, and claudin-3 in the small intestine while decreasing the serum diamine oxidase (DAO) and D-lactate levels in weaning piglets. Meanwhile, T1 and T2 treatments significantly increased the positive rate of proliferating cell nuclear antigen (PCNA) of the small intestine, promoting intestinal cell proliferation. We also found that supplementation with glu, gln, and asp improved the serum amino acid pool and promoted ileal amino acid transporter gene expression of slc3a2, slc6a14, and slc7a11 in weaned piglets. Additionally, on day 21 post-weaning, T1 and T2 treatments stimulated the phosphorylation of the mTOR-S6K1-4EBP1 signaling pathway in the small intestine, which may implicate the enhanced protein synthesis rate. In summary, dietary supplementation of gln, glu, and asp was beneficial to the intestinal barrier function and amino acid pool regulation, while the benefits of gln, glu, and asp treatment might be diminished by the low-energy diet. The results demonstrated that the supplementation of gln, glu, and asp under low energy levels was preferentially supplied as the energy fuel to restore the gut barrier function in piglets on day 5 post-weaning. With the increase in age and intestinal maturation (on day 21 post-weaning), gln, glu, and asp supplementation could also show an effect on the regulation of the amino acid pool and protein synthesis.

BackgroundAtaxia-telangiectasia (A-T) is a multisystem genetic disorder involving ataxia, oculocutaneous telangiectasia, and immunodeficiency caused by biallelic pathogenic variants in the ATM gene. To date, most ATM variants have been reported in the Caucasian population, and few studies have focused on the genotype–phenotype correlation of A-T in the Chinese population. We herein present a Chinese patient with A-T who carries compound heterozygous variants in the ATM gene and conducted a literature review for A-T in China.Case presentationA 7-year-old Chinese girl presented with growth retardation, ataxia, medium ocular telangiectasia, cerebellar atrophy, and elevated serum alpha-fetoprotein (AFP) level, which supported the suspicion of A-T. Notably, the serum levels of immunoglobulins were all normal, ruling out immunodeficiency. Exome sequencing and Sanger sequencing revealed two likely pathogenic ATM variants, namely NM_000051.4: c.4195dup (p.Thr1399Asnfs*15) and c.6006 + 1G>T (p.?), which were inherited from her father and mother, respectively. From the Chinese literature review, we found that there was a marked delay in the diagnosis of A-T, and 38.9% (7/18) of A-T patients did not suffer from immunodeficiency in China. No genotype–phenotype correlation was observed in this group of A-T patients.ConclusionThese results extend the genotype spectrum of A-T in the Chinese population and imply that the diagnosis of A-T in China should be improved.

Exploring the geological factors that affect fluid flow has always been a hot topic. For tight reservoirs, the pore structure and characteristics of different lithofacies reveal the storage status of fluids in different reservoir environments. The size, connectivity, and distribution of fillers in different sedimentary environments have always posed a challenge in studying the microscopic heterogeneity. In this paper, six logging curves (gamma-ray, density, acoustic, compensated neutron, shallow resistivity, and deep resistivity) in two marker wells, namely, J1 and J2, of the Permian Lucaogou Formation in the Jimsar Basin are tested by using four reinforcement learning algorithms: LogitBoost, GBM, XGBoost, and KNN. The total percent correct of training well J2 is 96%, 96%, 96%, and 96%, and the total percent correct of validation well J1 is 75%, 68%, 72%, and 75%, respectively. Based on the lithofacies classification obtained by using reinforcement learning algorithm, micropores, mesopores, and macropores are comprehensively described by high-pressure mercury injection and low-pressure nitrogen gas adsorption tests. The multifractal theory servers for the quantitative characterization of the pore distribution heterogeneity regarding different lithofacies samples, and as observed, the higher probability measure area of the generalized fractal spectrum affects the heterogeneity of the local interval of mesopores and macropores of the estuary dam. In the micropore and mesopore, the heterogeneity of the evaporation lake showed a large variation due to the influence of the higher probability measure area, and in the mesopore and macropore, the heterogeneity of the evaporation lake was controlled by the lower probability measure area. According to the correlation analysis, the single-fractal dimension is well related to the multifractal parameters, and the individual fitting degree reaches up to 99%, which can serve for characterizing the pore size distribution uniformity. The combination of boosting machine learning and multifractal can help to better characterize the micro-heterogeneity under different sedimentary environments and different pore size distribution ranges, which is helpful in the exploration and development of oil fields.

BackgroundHeart failure is a common cardiovascular disease that imposes a heavy clinical and economic burden worldwide. Previous research and guidelines have supported exercise training as a safe, effective, and cost-efficient treatment to intervene in heart failure. The aim of this study was to analyze the global published literature in the field of exercise training for heart failure from 2002 to 2022, and to identify hot spots and frontiers within this research field.MethodsBibliometric information on literature on the topic of exercise training for heart failure published between 2002 and 2022 was searched and collected in the Web of Science Core Collection. CiteSpace 6.1.R6 (Basic) and VOSviewer (1.6.18) were applied to perform bibliometric and knowledge mapping visualization analyses.ResultsA total of 2017 documents were retrieved, with an upward-stable trend in the field of exercise training for heart failure. The US authors were in the first place with 667 documents (33.07%), followed by Brazilian authors (248, 12.30%) and Italian authors (182, 9.02%). The Universidade de São Paulo in Brazil was the institution with the highest number of publications (130, 6.45%). The top 5 active authors were all from the USA, with Christopher Michael O'Connor and William Erle Kraus publishing the most documents (51, 2.53%). The International Journal of Cardiology (83, 4.12%) and the Journal of Applied Physiology (78, 3.87%) were the two most popular journals, while Cardiac Cardiovascular Systems (983, 48.74%) and Physiology (299, 14.82%) were the two most popular categories. Based on the results of keyword co-occurrence network and co-cited reference network, the hot spots and frontiers of research in the field of exercise training for heart failure were high-intensity interval training, behaviour therapy, heart failure with preserved ejection fraction, and systematic reviews.ConclusionThe field of exercise training for heart failure has experienced two decades of steady and rapid development, and the findings of this bibliometric analysis provide ideas and references for relevant stakeholders such as subsequent researchers for further exploration.

The physics potential of detecting ^8 B solar neutrinos will be exploited at the Jiangmen Underground Neutrino Observatory (JUNO), in a model-independent manner by using three distinct channels of the charged current (CC), neutral current (NC), and elastic scattering (ES) interactions. Due to the largest-ever mass of ^13 C nuclei in the liquid scintillator detectors and the expected low background level, ^8 B solar neutrinos are observable in the CC and NC interactions on ^13 C for the first time. By virtue of optimized event selections and muon veto strategies, backgrounds from the accidental coincidence, muon-induced isotopes, and external backgrounds can be greatly suppressed. Excellent signal-to-background ratios can be achieved in the CC, NC, and ES channels to guarantee the observation of the ^8 B solar neutrinos. From the sensitivity studies performed in this work, we show that JUNO, with 10 yr of data, can reach the 1 σ precision levels of 5%, 8%, and 20% for the ^8 B neutrino flux, ${\sin }^{2}{\theta }_{12}$ , and ${\rm{\Delta }}{m}_{21}^{2}$ , respectively. Probing the details of both solar physics and neutrino physics would be unique and helpful. In addition, when combined with the Sudbury Neutrino Observatory measurement, the world's best precision of 3% is expected for the measurement of the ^8 B neutrino flux.

The wings of birds exhibit multi-degree-of-freedom motions during flight. Among them, the flapping folding motion and chordwise passive deformation of the wings are prominent features of large birds in flight, contributing to their exceptional flight capabilities. This article presents a method for the fast and accurate calculation of folding passive torsional flapping wings in the early design stage. The method utilizes the unsteady three-dimensional panel method to solve the aerodynamic force and the linear beam element model to analyze the fluid–structure coupling problem. Performance comparisons of folding flapping wings with different kinematics are conducted, and the effects of various kinematic parameters on folding flapping wings are analyzed. The results indicate that kinematic parameters significantly influence the lift coefficient, thrust coefficient, and propulsion efficiency. Selecting the appropriate kinematic and geometric parameters is crucial for enhancing the efficiency of the folding flapping wing.

For large bird-like flapping wing aircraft, the fluid–structure coupling problem is very important. Through the passive torsional deformation of the wing, sufficient thrust is generated and propulsion efficiency is ensured. Moreover, spanwise bending deformation will affect lift and thrust. The flow field on the surface of the wing and the geometric nonlinearity caused by the large deformation of the wing should be considered during the design process. Existing research methods do not solve this problem accurately and efficiently. This paper provides a method to analyze the fluid–structure coupling problem of the flapping wing which adopts the three-dimensional unsteady panel method to solve the aerodynamic force, and adopts the linear beam element model combined with the corotational formulation method to consider the geometric nonlinear deformation of the wing beam. This article compares the performance of the flapping wing with different torsional and bending stiffness, and analyzes the airfoil surface pressure coefficients at different portions of the wing during the period. The results show that torsional stiffness has a large influence on the lift coefficient, thrust coefficient and propulsion efficiency. Meanwhile, the torsional stiffness of the wing beam and the initial geometric twist angle of the wing need to be well coordinated to achieve high efficiency. Moreover, appropriate bending stiffness of the wing is conducive to improving propulsion efficiency.

The flight of a migratory bird-like flapping-wing aircraft is characterized by a low Reynolds number and unsteadiness. The selection of airfoil profiles is critical to designing an efficient flapping-wing aircraft. To choose the suitable airfoil for various wing sections, it is necessary to calculate the aerodynamic forces of the unsteady two-dimensional airfoil with a Reynolds number in the range of 105. While accurate, calculating this by solving the Navier–Stokes equations is impractical for early design stages due to its high consumption of computing resources and time. The computational demands for extending it to 3D aerodynamic calculations are even more prohibitive. In this paper, a relatively simple method is proposed. The two-dimensional unsteady panel method is utilized to derive the inviscid flow field, the unsteady integral boundary layer method is utilized to solve the boundary layer viscous flow, and the eN transition model is adopted to predict the position of the transition. These models are coupled with the semi-inverse interaction method to solve the aerodynamics of the unsteady low-Reynolds-number two-dimensional airfoil. The unsteady aerodynamics of the symmetric and cambered airfoils at different wing sections are calculated respectively by the proposed method. Mechanism analysis of the calculation results is conducted, and a symmetrical airfoil or a slightly cambered airfoil is recommended for the wing tip, a moderately cambered airfoil is suggested for the outer-wing section, and a highly cambered airfoil is suggested for the inner-wing section.

Abstract We study damping signatures at the Jiangmen Underground Neutrino Observatory (JUNO), a medium-baseline reactor neutrino oscillation experiment. These damping signatures are motivated by various new physics models, including quantum decoherence, ν 3 decay, neutrino absorption, and wave packet decoherence. The phenomenological effects of these models can be characterized by exponential damping factors at the probability level. We assess how well JUNO can constrain these damping parameters and how to disentangle these different damping signatures at JUNO. Compared to current experimental limits, JUNO can significantly improve the limits on τ 3/m 3 in the ν 3 decay model, the width of the neutrino wave packet σ x , and the intrinsic relative dispersion of neutrino momentum σ rel.

BackgroundCat eye syndrome (CES) is a rare disease with a wide spectrum of phenotypic variability that is observed in 1:150,000 newborns. CES is characterized clinically by the combination of iris coloboma, anal atresia, and preauricular tags and/or pits. Many eye malformations have been reported to be associated with CES, such as iris and chorioretinal coloboma. However, an abnormality of eye movement has not been previously reported.Case presentationWe report on a Chinese family carrying a 22q11.1-q11.21 duplication of 1.7Mb tetrasomy (chr22:16,500,000–18,200,000, hg38) in two generations. Based on the proband and her father’s clinical manifestations, including ophthalmological examination, cytogenetic analysis, FISH, CNV-seq, and WES, the diagnosis of CES with an abnormality of eye movement was made.ConclusionOur findings broadened the symptom spectrum of CES syndrome and laid the foundation for pathogenesis, diagnostic targets, and drug research on the abnormality of eye movement, and were helpful for early diagnosis and intervention of CES.

Weaning stress may cause reduced energy intake for maintenance of mucosal structure. Gln, Glu, and Asp are major energy sources for the small intestine. This study investigated whether Gln, Glu, and Asp improve the intestinal morphology via regulating the energy metabolism in weaning piglets. A total of 198 weaned piglets were assigned to 3 treatments: Control (Basal diet + 1.59% L-Ala); T1 (Basal diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp); T2 (Low energy diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp). Jejunum and ileum were obtained on d 5 or 21 post-weaning. T1 enhanced growth performance. T1 and T2 treatments improved small intestinal morphology by increasing villus height, goblet cell number and decreasing crypt depth. Days post-weaning affected the efficacy of T2, but not T1, on energy metabolism. At normal energy supplementation, Gln, Glu, and Asp restored small intestinal energy homeostasis via replenishing the Krebs' cycle and down-regulating the AMPK (adenosine monophosphate activated protein kinase) pathway. As these are not sufficient to maintain the intestinal energy-balance of piglets fed with a low energy diet on d 5 post-weaning, the AMPK, glycolysis, beta-oxidation, and mitochondrial biogenesis are activated to meet the high energy demand of enterocytes. These data indicated that Gln, Glu, and Asp could restore the energy homeostasis of intestinal mucosa of weaning piglets under normal energy fed. Low energy feeding may increase the susceptibility of piglets to stress, which may decrease the efficacy of Gln, Glu, and Asp on the restoration of energy balance. These findings provide new information on nutritional intervention for insufficient energy intake in weaning piglets.

Over the past few years, China has become a hotspot for the domestication of the commercially valuable largemouth bass (Micropterus salmoides). Although the food preference of this fish has been studied, little is known about the genes regulating its growth. Population breeding was performed using two indigenous strains (QT1 and QT2), with the results showing that the organ/body ratio, abdominal fat rate and the body weight gain of QT1 and QT2 were higher than for the offspring YL1 and Y3 which are extensively cultured in China. Subsequent RNA sequencing (RNA-Seq) allowed for the identification of potential genes and pathways involved in growth performance. Overall, the transcriptome analysis generated 89,056 transcripts and 42,529 Unigenes. A PCA revealed significant differences between QT1 and the other three strains, while the other three strains did not show much difference. A KEGG enrichment analysis of differentially expressed genes showed that steroid biosynthesis was the most enriched pathway among the four strains. These pathways could be related to the growth of largemouth bass. In addition, a co-expression network analysis suggested a strong interaction between liver steroid biosynthesis and the genes for photosynthesis, secondary metabolism and stress response. Taken together, the above results can provide new insights into the liver metabolism of different strains of largemouth bass during culture and provide references for the subsequent domestication and breeding programs of largemouth bass.

Abstract Background Gut health plays a vital role in the overall health and disease control of human and animals. Intestinal oxidative stress is a critical player in the induction and progression of cachexia which is conventionally diagnosed and classified by weight loss. Therefore, reduction of intestinal oxidative injury is a common and highly effective strategy for the maintenance of human and animal health. Here we identify intestinal myeloid differentiation primary response gene 88 (MyD88) as a novel target for intestinal oxidative stress using canonical oxidative stress model induced by paraquat (PQ) in vitro and in vivo. Methods Intestinal oxidative stress was induced by administration of PQ in intestinal epithelial cells (IECs) and mouse model. Cell proliferation, apoptosis, DNA damage, mitochondrial function, oxidative status, and autophagy process were measured in wild‐type and MyD88‐deficient IECs during PQ exposure. Autophagy inhibitor (3‐methyladenine) and activator (rapamycin) were employed to assess the role of autophagy in MyD88‐deficient IECs during PQ exposure. MyD88 specific inhibitor, ST2825, was used to verify function of MyD88 during PQ exposure in mouse model. Results MyD88 protein levels and apoptotic rate of IECs are increased in response to PQ exposure (P

Abstract Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs. Graphical abstract Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.

Abstract As the promising and highly‐focused materials after silicon, carbon, and phosphorus promote the development of nanotechnology due to its allotropes with unique structures and properties. The carbon allotropes of 0D fullerene, 1D carbon nanotube, and 2D graphene stimulate the investigation of structures, synthesis, properties, and further applications of carbon nanomaterials. Analogous to carbon, phosphorus is demonstrated to have a rich phase diagram. 0D phosphorus fullerenes, 1D phosphorus nanotubes and fibrous red phosphorus, and recently 2D black phosphorene and violet phosphorene have unique structures analogous to carbon fullerene, carbon nanotube, and graphene, is developed. The photoelectronic properties and further applications of the phosphorus allotropes as semiconductors, energy storage materials, biomaterials, and sensors are also investigated. Great efforts are dedicated to studies of the synthesis, structure, and properties of carbons and phosphorus. However, there is no systematic review of the structure of phosphorus allotropes compared to carbon allotropes. Herein, the structures along with possible future perspective of carbon and phosphorus allotropes review and compare in this work based on the classification of different dimensions.

Introduction: Bone morphogenetic proteins (BMPs) play a crucial role in bone formation and differentiation. Recent RNA-Seq results suggest that BMPs may be involved in the sex differentiation of P. sinensis, yet more relevant studies about BMPs in P. sinensis are lacking.Methods: Herein, we identified BMP gene family members, analyzed the phylogeny, collinear relationship, scaffold localization, gene structures, protein structures, transcription factors and dimorphic expression by using bioinformatic methods based on genomic and transcriptomic data of P. sinensis. Meanwhile, qRT-PCR was used to verify the RNA-Seq results and initially explore the function of the BMPs in the sex differentiation of P. sinensis.Results: A total of 11 BMP genes were identified, 10 of which were localized to their respective genomic scaffolds. Phylogenetic analysis revealed that BMP genes were divided into eight subfamilies and shared similar motifs (“WII”, “FPL”, “TNHA”, “CCVP”, and “CGC”) and domain (TGF-β superfamily). The results of the sexually dimorphic expression profile and qRT-PCR showed that Bmp2, Bmp3, Bmp15l, Bmp5, Bmp6 and Bmp8a were significantly upregulated in ovaries, while Bmp2lb, Bmp7, Bmp2bl and Bmp10 were remarkable upregulated in testes, suggesting that these genes may play a role in sex differentiation of P. sinensis.Discussion: Collectively, our comprehensive results enrich the basic date for studying the evolution and functions of BMP genes in P. sinensis.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of global mortality, with numerous factors influencing the patient survival rate and prognosis. This study aimed to evaluate the OHCA epidemiology in China and elaborate on the current Hangzhou emergency system status. This retrospective analysis was based on the medical history system of the Hangzhou Emergency Center registered from 2015-2021. We provided a detailed description of OHCA characteristics and investigated the factors affecting the success rate of emergency treatment in terms of epidemiology, causes of onset, bystander rescue, and outcome factors. We included 9585 out-of-hospital cardiac arrest cases, of which 5442 (56.8%) had evidence of resuscitation. Patients with underlying diseases constituted the vast majority (80.1%); trauma and physicochemical factors accounted for 16.5% and 3.4%, respectively. Only 30.4% of patients (about 80.0% of bystanders witnessed) received bystander first aid. The outcome rate of emergency doctors dispatched by emergency centres was significantly higher than doctors dispatched by hospitals. Additionally, physician's first-aid experience, emergency response time, emergency telephone availability, initial heart rhythm, out-of-hospital defibrillation, out-of-hospital intubation, and using of epinephrine significantly can significantly improve the out-of-hospital return of spontaneous circulation in patients. All steps in pre-hospital care are important for patients, especially for bystander first aid and physician's first-aid experience. The popularity of first-aid training and the public emergency medical system are not potent enough. We should take those key factors into consideration when developing a pre-hospital care system for OHCA.

Primary ovarian insufficiency (POI) is among the foremost causes of women infertility due to premature partial or total loss of ovarian function. Resistant ovary syndrome (ROS) is a subtype of POI manifested as normal ovarian reserve but insensitive to gonadotropin stimulation. Inactivating variants of follicle-stimulating hormone receptor (FSHR), a class A G-protein coupled receptor, have been associated with POI and are inherited via an autosomal recessive pattern. In this study, we investigated the genetic causes of a primary infertility patient manifested as POI with ROS, and elucidated the structural and functional impact of variants of uncertain significance. Next-generation sequencing (NGS) combined with Sanger sequencing revealed novel compound heterozygous FSHR variants: c.1384G>C/p.Ala462Pro and c.1862C>T/p.Ala621Val, inherited from her father and mother, respectively. The two altered amino acid sequences, localized in the third and seventh transmembrane helix of FSHR, were predicted as deleterious by in silico prediction. In vitro experiments revealed that the p.Ala462Pro variant resulted in barely detectable levels of intracellular signaling both in cAMP-dependent CRE-reporter activity and ERK activation and displayed a severely reduced plasma membrane receptor expression. In contrast, the p.Ala621Val variant resulted in partial loss of receptor activation without disruption of cell surface expression. In conclusion, two unreported inactivating FSHR variants potentially responsible for POI with ROS were first identified. This study expands the current phenotypic and genotypic spectrum of POI.

Abstract Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder. Severe OSAS defined as apnea–hypopnea index (AHI) ≥ 30/h is a risk factor for developing cerebro-cardiovascular diseases. The mechanisms of how repetitive sleep apneas/hypopneas damage cerebral hemodynamics are still not well understood. In this study, changes in blood volume (BV) and oxygen saturation (StO2) in the left forehead of 29 newly diagnosed severe OSAS patients were measured by frequency-domain near-infrared spectroscopy during an incremental continuous positive airway pressure (CPAP) titration protocol together with polysomnography. The coefficients of variation of BV (CV-BV) and the decreases of StO2 (de-StO2) of more than 2000 respiratory events were predicted using linear mixed-effect models, respectively. We found that longer events and apneas rather than hypopneas induce larger changes in CV-BV and stronger cerebral desaturation. Respiratory events occurring during higher baseline StO2 before their onsets, during rapid-eye-movement sleep and those associated with higher heart rate induce smaller changes in CV-BV and de-StO2. The stepwise increased CPAP pressures can attenuate these changes. These results suggest that in severe OSAS the length and the type of respiratory event rather than widely used AHI may be better parameters to indicate the severity of cerebral hemodynamic changes.

Abstract The OSIRIS detector is a subsystem of the liquid scintillator filling chain of the JUNO reactor neutrino experiment. Its purpose is to validate the radiopurity of the scintillator to assure that all components of the JUNO scintillator system work to specifications and only neutrino-grade scintillator is filled into the JUNO Central Detector. The aspired sensitivity level of $$10^{-16}\hbox { g/g}$$ 10 - 16 g/g of $$^{238}\hbox {U}$$ 238 U and $$^{232}\hbox {Th}$$ 232 Th requires a large ( $$\sim 20\,\hbox {m}^3$$ ∼ 20 m 3 ) detection volume and ultralow background levels. The present paper reports on the design and major components of the OSIRIS detector, the detector simulation as well as the measuring strategies foreseen and the sensitivity levels to U/Th that can be reached in this setup.

Abstract JUNO is a massive liquid scintillator detector with a primary scientific goal of determining the neutrino mass ordering by studying the oscillated anti-neutrino flux coming from two nuclear power plants at 53 km distance. The expected signal anti-neutrino interaction rate is only 60 counts per day (cpd), therefore a careful control of the background sources due to radioactivity is critical. In particular, natural radioactivity present in all materials and in the environment represents a serious issue that could impair the sensitivity of the experiment if appropriate countermeasures were not foreseen. In this paper we discuss the background reduction strategies undertaken by the JUNO collaboration to reduce at minimum the impact of natural radioactivity. We describe our efforts for an optimized experimental design, a careful material screening and accurate detector production handling, and a constant control of the expected results through a meticulous Monte Carlo simulation program. We show that all these actions should allow us to keep the background count rate safely below the target value of 10 Hz (i.e. ∼1 cpd accidental background) in the default fiducial volume, above an energy threshold of 0.7 MeV.