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Abstract Chlorinated organic pollutants widely exist in aquatic environments and threaten human health. Catalytic approaches are proposed for their elimination, but sluggish degradation, incomplete dechlorination, and catalyst recovery remain extremely challenging. Here we show efficient dechlorination using ferrous oxide/graphene oxide catalytic membranes with strong nanoconfinement effects. Catalytic membranes are constructed by graphene oxide nanosheets with integrated ultrafine and monodisperse sub-5 nm nanoparticles through simple in-situ growth and filtration assembly. Density function theory simulation reveals that nanoconfinement effects remarkably reduce energy barriers of rate-limiting steps for iron (III)-sulfite complex dissociation to sulfite radicals and dichloroacetic acid degradation to monochloroacetic acid. Combining with nanoconfinement effects of enhancing reactants accessibility to catalysts and increasing catalyst-to-reactant ratios, the membrane achieves ultrafast and complete dechlorination of 180 µg L−1 dichloroacetic acid to chloride, with nearly 100% reduction efficiency within a record-breaking 3.9 ms, accompanied by six to seven orders of magnitude greater first-order rate constant of 51,000 min−1 than current catalysis. Meanwhile, the membranes exhibit quadrupled permeance of 48.6 L m−2 h−1 bar−1 as GO ones, because nanoparticles adjust membrane structure, chemical composition, and interlayer space. Moreover, the membranes show excellent stability over 20 cycles and universality for chlorinated organic pollutants at environmental concentrations.

Objective Air pollution is increasing and threatening human health. The objective of this study is to investigate the population distribution characteristics of elderly osteoporosis fractures in Hebei Province and Xinjiang Uygur Autonomous Region and to analyze the effects of air pollutants on the number of elderly osteoporosis fracture inpatients in the two regions. Method A retrospective collection of elderly osteoporosis fracture cases was conducted in selected hospitals in Hebei Province and Xinjiang Uygur Autonomous Region from January 1, 2018 to December 31, 2022. The chi‐square test was used to compare the distributional characteristics of the population in the two regions. Additionally, we used a distributed lag nonlinear model (DLNM) in order to assess the effect of air pollutants on the number of daily hospital admissions of elderly osteoporosis fracture patients in different regions. Result A total of 19,203 elderly osteoporosis fracture patients were included in the study. The average age of these patients was 76.66 ± 7.55 years, and the majority of them were female (13,514 instances, 70.37%). The disparities in age distribution (χ2 = 133.9 p

Abstract This study aims to identify colorectal cancer (CRC)-related proteomic profiles and develop a prediction model for CRC onset by integrating proteomic profiles with genetic and non-genetic factors (QCancer-15) to improve the risk stratification and estimate of personalized initial screening age. Here, using a two-stage strategy, we prioritize 15 protein biomarkers as predictors to construct a protein risk score (ProS). The risk prediction model integrating proteomic profiles with polygenic risk score (PRS) and QCancer-15 risk score (QCancer-S) shows improved performance (C-statistic: 0.79 vs. 0.71, P = 4.94E–03 in training cohort; 0.75 vs 0.69, P = 5.49E–04 in validation cohort) and net benefit than QCancer-S alone. The combined model markedly stratifies the risk of CRC onset. Participants with high ProS, PRS, or combined risk score are proposed to start screening at age 46, 41, or before 40 years old. In this work, the integration of blood proteomics with PRS and QCancer-15 demonstrates improved performance for risk stratification and clinical implication for the derivation of risk-adapted starting ages of CRC screening, which may contribute to the decision-making process for CRC screening.

Abstract Background Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. Methods PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). Results The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02–1.12), prostate cancer (OR = 1.02, 95% CI = 1.00–1.05), leukemia (OR = 1.18, 95% CI = 1.13–1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12–1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16–6.71); and a linear dose–response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09–1.24), respectively. Conclusions Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.

Abstract This study aimed to compare the long-term outcomes of breast-conserving surgery plus radiotherapy (BCS + RT) and mastectomy in early breast cancer (EBC) patients who received neoadjuvant systemic therapy (NST), and sought to construct and authenticate a machine learning algorithm that could assist healthcare professionals in formulating personalized treatment strategies for this patient population. We analyzed data from the Surveillance, Epidemiology, and End Results database on EBC patients undergoing BCS + RT or mastectomy post-NST (2010–2018). Employing propensity score matching (PSM) to minimize potential biases, we compared breast cancer-specific survival (BCSS) and overall survival (OS) between the two surgical groups. Additionally, we trained and validated six machine learning survival models and developed a cloud-based recommendation system for surgical treatment based on the optimal model. Among the 13,958 patients, 9028 (64.7%) underwent BCS + RT and 4930 (35.3%) underwent mastectomy. After PSM, there were 3715 patients in each group. Compared to mastectomy, BCS + RT significantly improved BCSS (p

Abstract Background There is currently a lack of comprehensive evidence regarding the correlation between Alternate Mediterranean Diet (AMED) and the survival of patients with ovarian cancer (OC). This prospective cohort study first assessed the association of AMED, not only pre-diagnosis and post-diagnosis but also the change from pre-diagnosis to post-diagnosis with OC survival. Methods A total of 560 OC patients were included in the study, and their dietary intake was assessed using a reliable 111-item food frequency questionnaire. The overall survival (OS) of the patients was monitored through active follow-up and review of medical records until February 16th, 2023. Cox proportional hazard regression models were utilized to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). Results Out of the total 560 patients with OC, 211 (37.68%) succumbed during a median follow-up period of 44.40 months (interquartile range: 26.97–61.37). Comparative analysis indicated a significant association between the highest tertiles of pre-diagnosis (HR = 0.59; 95% CI 0.38–0.90; P trend

Non-alcoholic fatty liver disease (NAFLD) and sarcopenia are prevalent metabolic disorders in middle-aged and elderly populations, with overlapping pathogenic mechanisms. The liver and skeletal muscle secrete hepatokines and myokines, which play crucial roles in maintaining energy homeostasis by activating metabolic signaling pathways and mediating crosstalk in the muscleliver axis. This review explores the specific mechanisms by which myokines and hepatokines contribute to the pathogenesis of NAFLD and sarcopenia, aiming to elucidate the regulatory network between the liver and skeletal muscle.

Abstract How Cooper pairs form and condense has been the main challenge in the physics of copper-oxide high-temperature superconductors. Great efforts have been made in the ‘underdoped’ region of the phase diagram, through doping a Mott insulator or cooling a strange metal. However, there is still no consensus on how superconductivity emerges when electron-electron correlations dominate and the Fermi surface is missing. To address this issue, here we carry out high-resolution resonant inelastic X-ray scattering and scanning tunneling microscopy studies on prototype cuprates Bi2Sr2Ca0.6Dy0.4Cu2O8+δ near the onset of superconductivity, combining bulk and surface, momentum- and real-space information. We show that an incipient charge order exists in the antiferromagnetic regime down to 0.04 holes per CuO2 unit, entangled with a particle-hole asymmetric pseudogap. The charge order induces an intensity anomaly in the bond-buckling phonon branch, which exhibits an abrupt increase once the system enters the superconducting dome. Our results suggest that the Cooper pairs grow out of a charge-ordered insulating state, and then condense accompanied by an enhanced interplay between charge excitations and electron-phonon coupling.

Manual semen evaluation methods are subjective and time-consuming. In this study, a deep learning algorithmic framework was designed to enable non-invasive multidimensional morphological analysis of live sperm in motion, improve current clinical sperm morphology testing methods, and significantly contribute to the advancement of assisted reproductive technologies. We improved the FairMOT tracking algorithm by incorporating the distance and angle of the same sperm head movement in adjacent frames, as well as the head target detection frame IOU value, into the cost function of the Hungarian matching algorithm. For sperm morphology, we used the BlendMask segmentation method to segment individual sperm. SegNet was used to separate the head, midpiece, and principal piece comments from each sperm. Experienced in vivo sperm physicians confirmed a morphological accuracy percentage of 90.82%. A total of 1272 samples were collected from multiple tertiary hospitals for validation of the system, which were also evaluated by physicians. The results of our system were highly consistent with those of manual microscopy. This study realized the automated detection of progressive motility and morphology of sperm simultaneously, which is crucial for selection of morphologically normal and motile sperm for intracytoplasmic sperm injection.

The aged often have multimorbidity, which arises from the decline in organ functioning and heightened vulnerability to illnesses. Sarcopenia, an advancing and widespread skeletal muscle illness, has common risk factors with many chronic disorders that are common among this population. The simultaneous presence of many chronic conditions and age-related loss of muscle mass and strength, known as multimorbidity and sarcopenia respectively, often worsens physical weakness and functional impairment in older individuals, significantly compromising their overall well-being. While most current studies primarily focus on the connection between individual illnesses and sarcopenia, there is a lack of research that investigates the relationship between several health conditions and sarcopenia. This review examines the existing comprehension of the interaction between multimorbidity and sarcopenia, with the goal of identifying areas of limited information and proposing potential avenues for future research.

Abstract Endothelial dysfunction is crucial factor to the hypertension occurrence, and controversy remains regarding the effect of exercise on improving endothelial function in hypertensive patients. The authors used meta‐analysis to evaluate the intervention effect of exercise on endothelial function in hypertensive patients and to investigate exercise protocols that may have a greater intervention effect. A total of 37 studies and a total of 2801 participants were included. The results were as follows: endogenous nitric oxide (NO)[SMD = .89, 95% CI (.48, 1.30), p

Abstract Proper alignment of activity-rest and light–dark patterns allows for healthy bodily functions to occur at optimal times of the day. Disruptions to this alignment may cause poor sleep as well as physical, mental, and cognitive problems. The purpose of this cross-sectional study was to determine if poorer circadian alignment was associated with decreased cognitive functioning among older (> 60 years) participants in the National Health and Nutrition Examination Survey. We utilized actigraphy-based rest-activity and dark-light measurements to calculate phasor magnitude (strength of circadian alignment coupling) and phasor angle (phase difference between activity-rest and light–dark cycles). Multiple linear regression models were used to determine associations of phasor magnitude and angle with performance in various cognitive tests, including Digit Symbol Substitution Test score (DSSS), CERAD Savings Percentage (CSP), and Animal Fluency Test (AFT) score. The results showed that a lower phasor magnitude (which indicates decreased strength of alignment coupling between rest-activity and dark–light cycles) was significantly associated with decreased DSSS (indicating slower processing speed and poorer working memory) when controlling for many important sociodemographic factors. However, this association became non-significant when accounting for sleep duration and total physical activity. Phasor angle did not have a significant association with any of the cognitive scores. Overall, we provided evidence indicating that circadian alignment may be a predictor of cognitive performance. Future studies should investigate whether improving circadian alignment may improve cognitive function and prevent cognitive decline.

The chloride-induced stress corrosion cracking (CISCC) is one of the major integrity concerns in dry storage canisters made of austenitic stainless steels (ASSs). In this study, an advanced duplex stainless steel (DSS) with a composition of Fe–19Cr–4Ni-2.5Mo-4.5Mn (ADCS) was developed and its performance was compared with that of commercial ASS and DSS alloys. The chemical composition of ADCS was determined to obtain greater pitting and CISCC resistance as well as a proper combination of strength and ductility. Then, the thermomechanical processing (TMP) condition was applied, which resulted in higher strength than ASSs (304L SS and 316L SS) and better ductility than DSSs (2101 LDSS and 2205 DSS). The potentiodynamic polarization and electrochemical impedance spectra (EIS) results represented the better pitting corrosion resistance of ADCS compared to 304L SS and 316L SS by forming a better passive layer. The CISCC tests using four-point loaded specimens showed that cracks were initiated at 24 h for 304L SS and 144 h for 316L SS, while crack was not found until 1008 h for ADCS. Overall, the developed alloy, ADCS, showed better combination of CISCC resistance and mechanical properties as dry storage canister materials than commercial alloys.

Objective Dysphagia is highly prevalent worldwide, causing serious complications. Video-game based rehabilitation training can increase dysphagia patient motivation and adherence. However, the acceptance of video game systems by patients and healthcare providers is still not fully explored. This study aimed to explore the acceptance of the video game swallowing training system among potential users. Methods The in-depth interviews were conducted face-to-face between July and October 2023 at a rehabilitation center in China, with a sample size based on the principle of information saturation. Interviews were audio-recorded and transcribed verbatim, and the data were analyzed using theory-driven thematic analysis methods based on the technology acceptance model. Results A total of 19 participants participated in the interviews, which included 11 hospitalized dysphagia patients, three rehabilitation therapists, one doctor, and four nurses. Three themes and seven subthemes were identified. Sufficient training content, interesting interaction between the game and the rehabilitation training, intuitive page design, and efficient training modes were related to the usefulness of the system; user-friendly page design and simple interface could make it easier for participants to use the system. Overall, the availability of the video game system for use without geographical or time limitations led to a high level of participant intention to use the system, but it is still challenging to use it in the real world. Conclusions The results of the study showed that participants were generally accepted and willing to use the video game system for dysphagia rehabilitation training. The video game-based swallowing function training system can be helpful in assisting with dysphagia rehabilitation.

ObjectiveThe study aimed to understand the current situation of hospital nurses’ patient safety competence, identify potential categories, and analyze the distribution characteristics of demographic variables in each subgroup.MethodsA total of 1,996 nursing staff were selected to be included in this research using a convenience sampling method. A questionnaire survey was conducted using the Chinese version of the Patient Safety Ability Scale, and three dimensions of the Patient Safety Ability Rating Scale were used as explicit variables for potential profile analysis. The influencing factors of different potential profiles of nurses’ patient safety ability were analyzed using logistic regression analysis.ResultsThe safety ability of the 1,996 nurses could be categorized into three potential groups as follows: “ability risk group” (14.3%), “medium ability group” (32.9%), and “ability advantage group” (52.7%), with monthly income, participation in department training, self-learning, and love of nursing as the influencing factors.ConclusionThe overall patient safety ability of nurses is at an upper-middle level. The classification of nurses can be predicted by factors, such as monthly income, participation in department training, self-directed learning, and love of nursing. Nursing managers can formulate targeted interventions according to the influencing factors of potential profiles to improve nurses’ patient safety ability.

Background: Previous research showed that plant-based diets were correlated with male-productive health, but evidence regarding the association of this diet with teratozoospermia remains unclear. This study aimed to investigate the association between plant-based diets and teratozoospermia odds. Methods: We conducted a case-control study involving 146 patients with teratozoospermia and 581 healthy controls in the infertility clinics of the Center for Reproductive Medicine during June and December 2020. To evaluate dietary data for the included participants, a validated food frequency questionnaire was utilized. Odds ratios (ORs) and 95% confidence intervals (CIs) for the development of teratozoospermia related to the plant-based diets were employed using unconditional logistic regression. Results: Higher adherence to the overall plant-based diet index (PDI) was inversely associated with the odds of teratozoospermia (OR T3 vs. T1 = 0.56; 95 % CI = 0.33–0.94). Additionally, greater adherence to the healthful PDI (hPDI) was correlated with a lower odds of teratozoospermia (OR T3 vs. T1 = 0.56; 95 % CI = 0.34–0.90), whereas the null association of unhealthful PDI (uPDI) with teratozoospermia was observed (OR T3 vs. T1 = 1.15; 95 % CI = 0.70–1.91). Interestingly, uPDI was positively associated with the odds of teratozoospermia among men with age

Huangjing is becoming a new generation of crop. Polygonatum kingianum var. grandifolium (XHJ) is a variant of P. kingianum (DHJ), and they are treated as Huangjing. Unlike other Polygonatum species, the rhizome bud of XHJ can germinate both in spring and autumn, which contributes to its high rhizome yield. However, the molecular mechanism of the autumn shooting of XHJ was still unknown. In the present study, cellular observation, comparative targeted metabolome of phytohormones, and transcriptome analysis between XHJ and DHJ in autumn were conducted. Interestingly, ‘Diterpenoid biosynthesis’ (ko00904) and ‘Plant hormone signal transduction’ (ko04075) were commonly enriched by differentially accumulated phytohormones (DAPs) and differentially expressed genes (DEGs) in all tissues, which indicated the high auxin content, low cytokinin (CTK) content, and low abscisic acid/gibberellin (ABA/GA) ratio might contribute to the XHJ rhizome buds’ differentiation and germination in autumn. Moreover, according to the weighted gene co-expression network analysis (WCGNA), transcript factors (TFs) related to auxin, CTK, GA, and jasmonic acid (JA) metabolism were screened, such as AP2/ERFs, WRKY, and NAC, which deserve further research. In conclusion, we comprehensively illustrated the mechanism of XHJ natural autumn shooting through cytological, metabolic, and transcriptomic analysis, which improves our understanding of the high yield of XHJ rhizomes and the diversity of shooting mechanisms in Polygonatum to lay the foundation for the further development of the Huangjing industry.

This study was to examine the effects of fish oil on alcoholic brain damage in rats, focusing on the insulin signaling pathway. Thirty-six male Wistar rats were divided into control (Lieber-DeCarli control liquid diet), CF25 (control diet + 25 % fish oil substitution), CF57 (control diet + 57 % fish oil substitution), E (Lieber-DeCarli ethanol liquid diet), EF25 (ethanol diet + 25 % fish oil substitution), and EF57 (ethanol diet + 57 % fish oil substitution) groups. The behavioral test was also conducted. After 8 weeks, the E group exhibited brain damage, including nuclear-condensed pyramidal cells and positivity for ionized calcium-binding adaptor molecule 1 (Iba-1) antibody. The E group revealed the higher hippocampal insulin receptor substrate-1 (IRS-1) and hypothalamic glycogen synthase kinase 3β (GSK3β), while presented the lower hepatic IRS-1, hippocampal insulin-like growth factor-1 (IGF-1) receptor and glucose transporter 4 (GLUT4). After fish oil substitution, the brain nuclear condensation was attenuated and the hippocampal IRS-1 and hypothalamic GSK3β were significantly decreased.

While light at night (LAN) and noise levels have been linked to suboptimal sleep outcomes, little is known about the link between these factors and long-term suboptimal sleep trajectories. The current study examined the association of neighborhood LAN and nighttime noise with long-term sleep trajectories in a cohort of Black individuals and White individuals predominantly from low-income communities. We used data from the Southern Community Cohort Study (N = 28,759 Black individuals and 16,276 White individuals). Sleep duration was self-reported at baseline and after an average of five years of follow-up, based on which we constructed nine sleep trajectories: normal–normal (optimal, reference), short–short, long–long, short–long, long–short, normal–short, normal–long, short–normal, and long–normal. LAN and nighttime noise were derived from satellite imagery and model-based estimates, respectively. Multinomial logistic regression was used to determine the relationship between LAN and noise exposures and sleep trajectories. Higher exposures to LAN and nighttime noise were associated with multiple suboptimal long-term sleep trajectories. In the total sample, higher LAN was associated with higher odds of long–long (OR Q5 vs. Q1 = 1.23 (CI = 1.02, 1.48)) and long–short (OR = 1.35 (CI = 1.06, 1.72)) trajectories, while higher nighttime noise was associated with short–short (1.19 (1.07, 1.31)), long–short (1.31 (1.05, 1.64)), and normal–song (1.16 (1.01, 1.34)) trajectories. Black and White individual-specific results showed qualitatively similar patterns between Black individuals and White individuals, although we also observed suggestive evidence for Black–White individual differences. In conclusion, elevated LAN and nighttime noise levels were associated with various suboptimal long-term sleep trajectories. However, it is noteworthy that the light and noise measures in our study may not accurately reflect individual-level exposures, and residual confounding from other factors is a concern. Future studies should use more accurate exposure measurements, collect information on and control for a wider range of factors, and examine whether reductions in neighborhood light and noise levels may contribute to improved long-term sleep health.

Abstract Background Sarcopenia and multimorbidity are common in older adults, and most of the available clinical studies have focused on the relationship between specialist disorders and sarcopenia, whereas fewer studies have been conducted on the relationship between sarcopenia and multimorbidity. We therefore wished to explore the relationship between the two. Methods The study subjects were older patients (aged ≥ 65 years) who were hospitalized at the Department of Geriatrics of the First Affiliated Hospital of Chongqing Medical University between March 2016 and September 2021. Their medical records were collected. Based on the diagnostic criteria of the Asian Sarcopenia Working Group in 2019, the relationship between sarcopenia and multimorbidity was elucidated. Results 1.A total of 651 older patients aged 65 years and above with 2 or more chronic diseases were investigated in this study, 46.4% were suffering from sarcopenia. 2. Analysis of the relationship between the number of chronic diseases and sarcopenia yielded that the risk of sarcopenia with 4–5 chronic diseases was 1.80 times higher than the risk of 2–3 chronic diseases (OR 1.80, 95%CI 0.29–2.50), and the risk of sarcopenia with ≥ 6 chronic diseases was 5.11 times higher than the risk of 2–3 chronic diseases (OR 5.11, 95% CI 2.97–9.08), which remained statistically significant, after adjusting for relevant factors. 3. The Charlson comorbidity index was associated with skeletal muscle mass index, handgrip strength, and 6–meter walking speed, with scores reaching 5 and above suggesting the possibility of sarcopenia. 4. After adjusting for some covariates among 14 common chronic diseases in older adults, diabetes (OR 3.20, 95% CI 2.01–5.09), cerebrovascular diseases (OR 2.07, 95% CI 1.33–3.22), bone and joint diseases (OR 2.04, 95% CI 1.32–3.14), and malignant tumors (OR 2.65, 95% CI 1.17–6.55) were among those that still a risk factor for the development of sarcopenia. Conclusion In the hospitalized older adults, the more chronic diseases they have, the higher the prevalence of sarcopenia. When the CCI is 5, attention needs to be paid to the occurrence of sarcopenia in hospitalized older adults.

Abstract Background A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. Methods Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP—0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. Results After exclusion, thirty-six patients (36.11% female; age range: 60–76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p

ABSTRACT: Copy number variation (CNV) is a crucial component of genetic diversity in the genome, serving as the foundation for the genetic architecture and phenotypic variability of complex traits. In this study, we examined CNVs in the Danzhou (DZ) chicken, an indigenous breed exclusive to Hainan Province, China. By employing whole-genome resequencing data from 200 DZ chickens, we conducted a comprehensive genome-wide analysis of CNVs using CNVpytor and performed CNV-based genome-wide association studies (GWAS) on 6 body size traits, including body slope length (BSL), keel length (KeL), tibial length (TiL), tibial circumference (TiC), chest width (ChW), and chest depth (ChD) utilizing linear mixed model methods considering a genomic relationship matrix. We identified a total of 144,265 autosomal CNVs among the 200 individuals, comprising 67,818 deletions and 76,447 duplications. After merging these variants together, we obtained 4,824 distinct copy number variant regions, which accounted for approximately 20% of the chicken autosomal genome. Furthermore, we discovered several significantly associated CNV segments with body size traits located proximal to genes such as IHH, WNT6, WNT10A, LPR4, FZD2, WNT7B, and GNAS that have been extensively implicated in skeletal development and growth processes. These findings enhance our understanding of CNVs in chickens and their potential impact on body size traits by revealing candidate genes involved in the regulation of these traits. This establishes a solid framework for future studies and may prove particularly beneficial for exploring genetic structural variation in chickens.

Introduction: Research suggests that perceived neighborhood social environments (PNSE) may contribute to gender and race/ethnicity-based sleep disparities. Our study aimed to examine associations between PNSE factors and adolescents’ sleep patterns. As a secondary aim, we examined how gender and race/ethnic groups might moderate these associations. Method: Data came from the National Longitudinal Study of Adolescent to Adult Health (n = 5158; mean age=15.34 years). Four self-reported sleep outcomes were created: 1) sleep duration (hours/night), 2) short sleep (≥8 h [reference] vs

ABSTRACT: Danzhou chicken (DZ) is a local breed in China noted for its strong adaptability, roughage resistance, strong wildness, and delicious taste, thus containing important genetic resources. In this study, genome re-sequencing data was generated from 200 DZ chickens. Combined with previously generated data from 72 additional chickens across six other exotic and local breeds, these data were used to systematically evaluate the germplasm characteristics of DZ chickens from a genomic perspective. Unlike exotic breeds, both DZ and southern local chicken varieties exhibited high genetic diversity, and the genetic distance between DZ and southern local chickens was smaller than the genetic distance between DZ and exotic chickens. A reconstructed Neighbor-Joining phylogenetic tree indicated that all sampled populations clustered into single independent populations, with DZ chickens showing clear evidence of intra-population differentiation, forming 2 subpopulations. Principal component analysis and ADMIXTURE analysis showed that DZ was significantly different from other breeds. These results indicate that DZ is a unique genetic resource that is different from other southern native and exotic chickens. The results of the study will improve our understanding of the genetic structure and current status of the DZ breed, which is of great significance in promoting the conservation of genetic resources of DZ chickens and fostering breed innovations and genetic improvement.

Abstract The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population‐based evidence. To clarify this, we present a retrospective analysis of 5871 colorectal cancer (CRC) patients. Propensity score matching (PSM) was applied to harmonize age and sex disparities within HBV+ (n = 1696) and HBV‐ (n = 4175) groups and further within HBV+ subgroups of chronic (CHB, n = 474) and occult (OHB, n = 1222) infections. Our initial results indicated a significant association between HBV infection and synchronous colorectal liver metastasis (SYN‐CRLM); however, this association dissipated after PSM was employed to adjust for confounding variables. No significant association was observed between HBV infection and metachronous colorectal liver metastases (MET‐CRLM) both before and after PSM. Further analysis revealed that HBV replication status did not influence the incidence of CRLM. However, HBV+ participants demonstrated an increased incidence of metachronous extrahepatic metastases, particularly to the lungs. Our findings imply that neither past nor present HBV infection is significantly correlated with the occurrence of SYN‐CRLM or MET‐CRLM. The absence of an association between HBV replication status and CRLM incidence highlights the importance of incorporating a broader range of factors in the clinical management of CRLM beyond the status of HBV infection.

Background Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but in vivo research on this topic remains limited.Aims This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD.Methods This study enrolled 28 drug-naive adults with OCD aged 18–40 years and 16 healthy controls (HCs). Three-dimensional T1-weighted structural magnetic resonance imaging and 18F-SynVesT-1 positron emission tomography were conducted. Cognitive function was assessed using the Wisconsin Cart Sorting Test (WCST) in patients with OCD and HCs. Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction.Results Compared with HCs, patients with OCD showed reduced synaptic density in regions of the cortico-striato-thalamo-cortical circuit such as the bilateral putamen, left caudate, left parahippocampal gyrus, left insula, left parahippocampal gyrus and left middle occipital lobe (voxel p

Abstract Objectives Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. Methods We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. Results After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p

Abstract Background There is substantial evidence to support the use of several methods for preventing deep-vein thrombosis (DVT) following intracerebral hemorrhage (ICH). However, the extent to which these measures are implemented in clinical practice and the factors influencing patients’ receipt of preventive measures remain unclear. Therefore, we aimed to evaluate the rate of the early implementation of DVT prophylaxis and the factors associated with its success in patients with ICH. Methods This study enrolled 49,950 patients with spontaneous ICH from the Chinese Stroke Center Alliance (CSCA) between August 2015 and July 2019. Early DVT prophylaxis implementation was defined as an intervention occurring within 48 h after admission. Univariate and multivariate logistic regression analyses were conducted to identify the rate and factors associated with the implementation of early prophylaxis for DVT in patients with ICH. Results Among the 49,950 ICH patients, the rate of early DVT prophylaxis implementation was 49.9%, the rate of early mobilization implementation was 29.49%, and that of pharmacological prophylaxis was 2.02%. Factors associated with an increased likelihood of early DVT prophylaxis being administered in the multivariable model included receiving early rehabilitation therapy (odds ratio [OR], 2.531); admission to stroke unit (OR 2.231); admission to intensive care unit (OR 1.975); being located in central (OR 1.879) or eastern regions (OR 1.529); having a history of chronic obstructive pulmonary disease (OR 1.292), ischemic stroke (OR 1.245), coronary heart disease or myocardial infarction (OR 1.2); taking antihypertensive drugs (OR 1.136); and having a higher Glasgow Coma Scale (GCS) score (OR 1.045). Conversely, being male (OR 0.936), being hospitalized in tertiary hospitals (OR 0.778), and having a previous intracranial hemorrhage (OR 0.733) were associated with a lower likelihood of early DVT prophylaxis being administered in patients with ICH. Conclusions The implementation rate of early DVT prophylaxis among Chinese patients with ICH was subpar, with pharmacological prophylaxis showing the lowest prevalence. Various controllable factors exerted an impact on the implementation of early DVT prophylaxis in this population.

Abstract Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance.

Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.

BackgroundDefinitive concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with immune checkpoint inhibitors offers the best chance of cure for patients with stage III non-small cell lung cancer (NSCLC). A significant challenge in this regimen is the occurrence of acute severe lymphopenia (ASL), which can compromise treatment efficacy. Currently, there are no effective strategies for preventing and treating ASL. Shenglin decoction (SLD), a traditional Chinese herbal medicine formulation, has demonstrated preliminary efficacy in mitigating ASL. However, robust evidence from clinical trials and a clear understanding of its mechanism of action are still needed. This study aims to comprehensively assess the efficacy, safety, and underlying mechanisms of SLD in the prevention of ASL.MethodsThis prospective, dual-center, open-label, randomized controlled trial will enroll 140 stage III NSCLC patients. Participants will be randomly allocated in a 1:1 ratio to a control group or an experimental group. Both groups will undergo definitive CCRT. Alongside the commencement of CCRT, the experimental group will receive an additional oral SLD intervention for a duration of three months. The primary outcome is the incidence rate of ASL, defined as the proportion of patients who experience at least one instance of a total lymphocyte count falling below 0.5 × 10^9 cells/L within 3 months of initiating CCRT treatment. Additionally, 16S rRNA gene sequencing analysis of fecal samples to assess gut microbiota, as well as metabolomic analysis of fecal/blood samples, will be conducted to explore potential mechanisms.DiscussionThis study protocol aims to rigorously evaluate the efficacy and safety of SLD, as well as elucidate its mechanism of action in preventing ASL. Successful outcomes could establish SLD as an evidence-based intervention for ASL prevention in NSCLC patients undergoing CCRT.Trial RegistrationThe trial was registered at the Chinese Clinical Trials Registry (ChiCTR2300071788, https://www.chictr.org.cn/).

Background and objectivesEarly neurological deterioration (END) occurs in up to one-third of patients with acute ischemic stroke (AIS) and associated with poor outcome. The role of serum bilirubin in END remains controversial. This study aims to investigate the association of total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) with END.MethodsThis study was a cross-sectional retrospective study with 344 AIS patients enrolled. We retrospectively reviewed consecutive AIS patients with END through a medical record retrieval system and enrolled patients as control randomly from the AIS patients without END at the same period. The bilirubin levels were compared between the END group and No END group. The correlations of bilirubin with END were assessed according to the bilirubin tertiles on the cohort of different genders.ResultsIn women, as the bilirubin level increased, the occurrence of END showed an increasing trend. The linear association was significant based on the tertiles of all bilirubin types (TBIL p = 0.003; DBIL p = 0.025; IBIL p = 0.025), while in men no similar trend was observed. After adjustment for confounders, higher TBIL (p for trend 0.009) and DBIL (p for trend 0.033) levels were associated with increased risk of END in women. The adjusted OR for T3 relative to T1 was 5.240 (95% CI 1.496–18.347) in TBIL and 3.549 (95% CI 1.089–11.566) in DBIL. Multivariate logistic regression showed that DBIL was independently associated with END in women (OR 1.717, 95% CI 1.106–2.666). The study also found that DBIL was superior to TBIL and IBIL in prediction of END occurrence in women, with greater predictive value.DiscussionThere were gender differences in the relationship between bilirubin and END, and DBIL level was positively associated with END occurrence in women, not in men. DBIL had greater incremental predictive value for END than TBIL and IBIL.

Summary: Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p

Previous research suggests that mathematical models could serve as valuable tools for diagnosing or predicting diseases like diabetic kidney disease, which often necessitate invasive examinations for conclusive diagnosis. In the big-data era, there are several mathematical modeling methods, but generally, two types are recognized: conventional mathematical model and machine learning model. Each modeling method has its advantages and disadvantages, but a thorough comparison of the two models is lacking. In this article, we describe and briefly compare the conventional mathematical model and machine learning model, and provide research prospects in this field.

Average sleep duration in the United States declined in recent years, and the decline may be linked with many biopsychosocial factors. We examine how a set of biopsychosocial factors have differentially contributed to the temporal trends in self-reported sleep duration across racial groups between 2004-2005 and 2017–2018. Using repeated nationally representative cross-sections from the National Health Interview Survey, we decompose the influence of biopsychosocial factors on sleep duration trends into two components. One component corresponds to coefficient changes (i.e., changes in the associations between behaviors or exposures and sleep duration) of key biopsychosocial factors, and the other part accounts for the compositional changes (i.e., changes in the distributions of exposures) in these biopsychosocial factors during the study period. We reveal that changes in the coefficients of some biopsychosocial factors are more important than compositional changes in explaining the decline in sleep duration within each racial/ethnic group. Our findings highlight racial differences manifest across multiple biopsychosocial domains that are shifting in terms of association and composition. Methodologically, we note that the standard regression approach for analyzing temporal trends neglects the role of coefficient changes over time and is thus insufficient for fully capturing how biopsychosocial factors may have influenced the temporal patterns in sleep duration and related health outcomes.

Abstract Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

Liver functions are regulated by the circadian rhythm; however, whether a weakened circadian rhythm is associated with impaired liver function is unclear. This study aims to investigate the association of characteristics of rest–activity rhythms with abnormal levels of biomarkers of liver function. Data were obtained from the National Health and Nutrition Examination Survey 2011–2014. Seven rest–activity rhythm parameters were derived from 24 h actigraphy data using the extended cosine model and non-parametric methods. Multiple logistic regression and multiple linear regression models were used to assess the associations between rest–activity rhythm parameters and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transaminase (GGT), albumin and bilirubin. Weakened overall rhythmicity characterized by a lower F statistic was associated with higher odds of abnormally elevated ALP (ORQ1vs.Q5: 2.16; 95% CI 1.19, 3.90) and GGT (ORQ1vs.Q5: 2.04; 95% CI 1.30, 3.20) and abnormally lowered albumin (ORQ1vs.Q5: 5.15; 95% CI 2.14, 12.38). Similar results were found for a lower amplitude, amplitude:mesor ratio, interdaily stability and intradaily variability. Results were robust to the adjustment of confounders and cannot be fully explained by individual rest–activity behaviors, including sleep and physical activity. Weakened rest–activity rhythms were associated with worse liver function as measured by multiple biomarkers, supporting a potential role of circadian rhythms in liver health.

Abstract Declines in oral consumption and swallowing function are common reasons which may elevate the risk of malnutrition in the older adults. This study aimed to provide valuable information and contribute to the existing body of knowledge in this field as well as highlight the importance of a comprehensive assessment of oral health, swallowing function, and nutritional status in long-term care residents. This was a cross-sectional study. Thirty-nine participants were recruited from a nursing home. The comprehensive assessment was evaluated in participants, including oral health (Oral Health Assessment Tool (OHAT)), swallowing function (Functional Oral Intake Scale (FOIS) and Eating Assessment Tool (EAT)-10), and nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF). The average age of participants was 80.4 ± 11.7 years, and 46% of these older adults were found to be at the risk of malnutrition. There was a negative correlation between the OHAT and MNA-SF scores. In addition, subjects with poor oral health (OHAT score = 5~8), oral consumption of a modified diet (FOIS score = 4~6), and reduced swallowing function (EAT-10 score ≥ 3) were more likely to be at risk of malnutrition. A comprehensive evaluation of oral health and swallowing function was closely connected with the nutritional status of older nursing home dwellers.

Abstract Background Dysphagia can lead to serious complications such as aspiration and aspiration pneumonia, timely and effective rehabilitation training can improve the swallowing function of patients. However, the conventional rehabilitation training methods used in clinical settings have shortcomings such as poor adherence of patients. We present the study design of a randomized controlled trial that evaluated whether video-game based swallowing rehabilitation training can effectively improve swallowing in patients with dysphagia and whether it has additional benefits compared with conventional training methods to improve swallowing function and training compliance among patients with dysphagia. Methods A randomized controlled trial with 4 weeks of intervention and 4 weeks of follow-up will be conducted in a rehabilitation center in Beijing, China. We will enroll 78 patients aged 18–80 years with dysphagia. Participants will be randomly assigned to the experimental group (video-game based swallowing function training) and the control group (conventional swallowing function training). All participants will receive 30 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcome is swallowing function. Secondary outcomes include patients' quality of life, training compliance, and training satisfaction. Outcomes are assessed at baseline (pre-treatment), 4 weeks of treatment (post-treatment), and 8 weeks (follow-up), and the assessor is not aware of the participants’ grouping. Discussion The protocol describes a new rehabilitation training method for dysphagia, which involves participant eligibility recruitment, recruitment strategies, and data analysis plan. The results of the study will inform the rehabilitation training and clinical care management of swallowing function in patients with dysphagia. Trial registration ClinicalTrials.gov, NCT05978700. Registered on 28 July 2023.

Abstract Background Suboptimal rest-activity patterns in adolescence are associated with worse health outcomes in adulthood. Understanding sociodemographic factors associated with rest-activity rhythms may help identify subgroups who may benefit from interventions. This study aimed to investigate the association of rest-activity rhythm with demographic and socioeconomic characteristics in adolescents. Methods Using cross-sectional data from the nationally representative National Health and Nutrition Examination Survey (NHANES) 2011–2014 adolescents (N = 1814), this study derived rest-activity profiles from 7-day 24-hour accelerometer data using functional principal component analysis. Multiple linear regression was used to assess the association between participant characteristics and rest-activity profiles. Weekday and weekend specific analyses were performed in addition to the overall analysis. Results Four rest-activity rhythm profiles were identified, which explained a total of 82.7% of variance in the study sample, including (1) High amplitude profile; (2) Early activity window profile; (3) Early activity peak profile; and (4) Prolonged activity/reduced rest window profile. The rest-activity profiles were associated with subgroups of age, sex, race/ethnicity, and household income. On average, older age was associated with a lower value for the high amplitude and early activity window profiles, but a higher value for the early activity peak and prolonged activity/reduced rest window profiles. Compared to boys, girls had a higher value for the prolonged activity/reduced rest window profiles. When compared to Non-Hispanic White adolescents, Asian showed a lower value for the high amplitude profile, Mexican American group showed a higher value for the early activity window profile, and the Non-Hispanic Black group showed a higher value for the prolonged activity/reduced rest window profiles. Adolescents reported the lowest household income had the lowest average value for the early activity window profile. Conclusions This study characterized main rest-activity profiles among the US adolescents, and demonstrated that demographic and socioeconomic status factors may shape rest-activity behaviors in this population.

Abstract Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the “Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy”(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal – rs1491377616-LCE3C – links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables.

Abstract Background Goat is an important livestock worldwide, which plays an indispensable role in human life by providing meat, milk, fiber, and pelts. Despite recent significant advances in microbiome studies, a comprehensive survey on the goat microbiomes covering gastrointestinal tract (GIT) sites, developmental stages, feeding styles, and geographical factors is still unavailable. Here, we surveyed its multi-kingdom microbial communities using 497 samples from ten sites along the goat GIT. Results We reconstructed a goat multi-kingdom microbiome catalog (GMMC) including 4004 bacterial, 71 archaeal, and 7204 viral genomes and annotated over 4,817,256 non-redundant protein-coding genes. We revealed patterns of feeding-driven microbial community dynamics along the goat GIT sites which were likely associated with gastrointestinal food digestion and absorption capabilities and disease risks, and identified an abundance of large intestine-enriched genera involved in plant fiber digestion. We quantified the effects of various factors affecting the distribution and abundance of methane-producing microbes including the GIT site, age, feeding style, and geography, and identified 68 virulent viruses targeting the methane producers via a comprehensive virus-bacterium/archaea interaction network. Conclusions Together, our GMMC catalog provides functional insights of the goat GIT microbiota through microbiome-host interactions and paves the way to microbial interventions for better goat and eco-environmental qualities. Video Abstract

Abstract Background The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify candidate protein markers and therapeutic targets for colorectal cancer (CRC). Methods Protein quantitative trait loci (pQTLs) were derived from seven published genome-wide association studies (GWASs) on plasma proteome, and summary-level data were extracted for 4853 circulating protein markers. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (16,871 cases and 26,328 controls), the FinnGen cohort (4957 cases and 304,197 controls), and the UK Biobank (9276 cases and 477,069 controls). Colocalization and summary-data-based MR (SMR) analyses were performed sequentially to verify the causal role of candidate proteins. Single cell-type expression analysis, protein-protein interaction (PPI), and druggability evaluation were further conducted to detect the specific cell type with enrichment expression and prioritize potential therapeutic targets. Results Collectively, genetically predicted levels of 13 proteins were associated with CRC risk. Elevated levels of two proteins (GREM1, CHRDL2) and decreased levels of 11 proteins were associated with an increased risk of CRC, among which four (GREM1, CLSTN3, CSF2RA, CD86) were prioritized with the most convincing evidence. These protein-coding genes are mainly expressed in tissue stem cells, epithelial cells, and monocytes in colon tumor tissue. Two interactive pairs of proteins (GREM1 and CHRDL2; MMP2 and TIMP2) were identified to be involved in osteoclast differentiation and tumorigenesis pathways; four proteins (POLR2F, CSF2RA, CD86, MMP2) have been targeted for drug development on autoimmune diseases and other cancers, with the potentials of being repurposed as therapeutic targets for CRC. Conclusions This study identified several protein biomarkers to be associated with CRC risk and provided new insights into the etiology and promising targets for the development of screening biomarkers and therapeutic drugs for CRC.

Abstract Secernin-1 (SCRN1) is a regulator of exocytosis in mast cells. Recently, SCRN1 was reported to be correlated with the prognosis of colorectal cancer and gastric cancer, but its functional effects on oral squamous cell carcinoma (OSCC) remain unclear. Our aim was to explore the expression pattern and the migration and invasion effects of the newly identified SCRN1 in OSCC. Western blotting (WB) was performed to measure SCRN1 expression in human OSCC tissue samples and OSCC cell lines. The effects of SCRN1 on OSCC cell proliferation, invasion and migration were analyzed by cell counting kit-8 and Transwell assays. The expression levels of TGF-β, Smad3 and phosphorylated Smad3 (p-Smad3) were measured by WB. The secretion of matrix metalloproteinase (MMP)-2 and MMP-9 was determined by the enzyme-linked immunosorbent assay. The expression of SCRN1 was significantly elevated in OSCC tissues and cell lines. SCRN1 knockdown reduced the expression of TGF-β and p-Smad3 in OSCC cells. TGF-β stimulation promoted proliferation, invasion and migration and enhanced the expression of p-Smad3 and the secretion of MMP9 in SCRN1-knockdown OSCC cell lines. Our study demonstrated that SCRN1 is upregulated in OSCC. Further analyses demonstrated that SCRN1 promotes the proliferation, invasion and migration of OSCC cells via TGF-β/Smad3 signaling.

Collaborative inhibition is a counterintuitive phenomenon. While the specific mechanisms through which social factors influence collaborative inhibition remain unclear, this study aims to shed light on the impact of gender, relationships, and culture in order to better understand the factors shaping collaborative inhibition. A meta-analysis was conducted to analyze subgroups of social factors, including collaborative pairing, gender, membership, and culture, as well as cognitive factors like memory monitoring. Collaborative inhibition was found to be a robust effect (p < 0.01), with moderating effects of pairing on gender (p < 0.01), membership (p < 0.01), culture (p < 0.01), and memory monitoring (p < 0.01). The findings indicate that collaborative inhibition is a consistent phenomenon influenced by both social and cognitive factors. Moreover, the study discovered that memory monitoring can successfully moderate collaborative inhibition, although the underlying mechanism requires further investigation.

Maintaining agricultural machinery is crucial for efficient mechanized farming. Specifically, diagnosing faults in rolling bearings, which are essential rotating components, is of significant importance. Domain-adaptive technology often addresses the challenge of limited labeled data from a single source domain. However, information transfer can sometimes fall short in providing adequate relevant details for supporting target diagnosis tasks, leading to poor recognition performance. This paper introduces a novel fault diagnosis model based on a multi-source locally adaptive graph convolution network to diagnose rolling bearing faults in agricultural machinery. The model initially employs an overlapping sampling method to enhance sample data. Recognizing that two-dimensional time–frequency signals possess richer spatial characteristics in neural networks, wavelet transform is used to convert time series samples into time–frequency graph samples before feeding them into the feature network. This approach constructs a sample data pair from both source and target domains. Furthermore, a feature extraction network is developed by integrating the strengths of deep residual networks and graph convolutional networks, enabling the model to better learn invariant features across domains. The locally adaptive method aids the model in more effectively aligning features from the source and target domains. The model incorporates a Softmax layer as the bearing state classifier, which is set up after the graph convolutional network layer, and outputs bearing state recognition results upon reaching a set number of iterations. The proposed method’s effectiveness was validated using a bearing dataset from Jiangnan University. For three different groups of bearing fault diagnosis tasks under varying working conditions, the proposed method achieved recognition accuracies above 99%, with an improvement of 0.30%-4.33% compared to single-source domain diagnosis models. Comparative results indicate that the proposed method can effectively identify bearing states even without target domain labels, showcasing its practical engineering application value.