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Abstract Introduction Previous randomized controlled trials (RCTs) and meta-analyses comparing Hemodiafiltration (HDF) with conventional hemodialysis (HD) on the effectiveness of HDF for mortality in end-stage renal disease (ESRD) patients have yielded contrasting results. Importantly, we sought to compile the available information to provide the most up-to-date and reliable evidence. Methods We systematically searched PubMed, Embase and Cochrane Library for RCTs up to January 14, 2024. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence. Results Our study involved 10 randomized controlled trials with 4654 chronic dialysis patients. Compared to hemodialysis, hemodiafiltration demonstrated a reduction in all-cause mortality (relative risk [RR] 0.84, 95% confidence intervals [CI] 0.72–0.99, P = 0.04) and cardiovascular mortality (RR 0.74, 95% CI 0.61–0.90, P = 0.002). However, it did not reduce the rate of sudden death (RR 0.92, 95% CI 0.64–1.34, P = 0.68) and infection-related mortality (RR 0.70, 95% CI 0.47–1.03, P = 0.07). A subgroup analysis revealed that HDF demonstrated superiority over high-flux hemodialysis in terms of all-cause mortality, while not over low-flux hemodialysis (RR 0.81, 95% CI 0.69–0.96, P = 0.01; RR 0.93, 95% CI 0.77–1.12, P = 0.44, respectively). Furthermore, a subgroup analysis for convection volume found that hemodiafiltration with a convection volume of 22 L or more reduced all-cause and cardiovascular mortality (RR 0.76, 95% CI 0.65–0.88, P = 0.0002, RR 0.73, 95% CI 0.54–0.94, P = 0.01, respectively). Conclusion In maintenance hemodialysis patients, hemodiafiltration can reduce mortality compared to conventional hemodialysis. Furthermore, this effect is more pronounced in HDF with high convection volume.

Abstract Background First-episode schizophrenia (FES) is a complex and progressive psychiatric disorder. The etiology of FES involves genetic, environmental, and neurobiological factors. This study investigates the association between alterations in structural–functional (SC-FC) coupling and transcriptional expression in FES. Methods This study encompassed a cohort of 214 participants, comprising 111 FES patients and 103 healthy controls (HC). Furthermore, we examined the abnormalities within SC-FC coupling in FES and their correlations with meta-analytic cognitive terms, neurotransmitters, and transcriptional patterns through partial least squares regression (PLS), involving similarity with other psychiatric disorders or psychiatric-related diseases, functional enrichments, special cell types, peripheral inflammation, and cortical layers. Results FES patients exhibited lower SC-FC coupling in the visual, sensorimotor, and ventral attention networks compared to controls. Furthermore, case–control t-maps revealed a negative correlation with neurotransmitters such as serotonin and dopamine, while showing a positive correlation with opioids. Positive t-maps were associated with cognitive functions, including reasoning, judgment, and action, whereas negative t-maps correlated with cognitive functions such as learning, stress, and mood. Moreover, there was a significant overlap between genes linked to abnormalities in SC-FC coupling and those dysregulated in inflammatory bowel diseases. PLS2- genes linked to SC-FC coupling demonstrated significant enrichment in pathways related to immunity and inflammation, as well as in cortical layers I and V. Conversely, PLS2 + genes were primarily enriched in synaptic signaling processes, specific excitatory neurons, and layers II and IV. Additionally, changes in SC-FC coupling were negatively associated with gene expression related to antipsychotics and lymphocytes. Conclusions These findings offer a new perspective on the complex interplay between SC-FC coupling abnormalities and transcriptional expression in the initial phases of schizophrenia.

Abstract The discovery of embryonic stem cell (ESC) mediating tumoricidal activity revealed the intimate relationship between ESCs and tumor cells, but the functional role of ESCs in tumor progression is poorly understood. To further investigate tumor cell and ESC interactions, we co-cultured mouse ESCs with mouse pancreatic cancer Pan02 cells or mouse melanoma B16-F10 cells in Transwell, and found that tumor cell invasion was significantly inhibited by ESCs. Application of ESCs to tumor-bearing mice resulted in significant inhibition of tumor metastasis in vivo. RNA-Seq analyses of tumor cell and ESC co-cultures identified TP53 and related signalling as major pathways involved in ESC-mediated inhibition of tumor cell invasion and metastasis, which indicated the potential clinical application of ESCs to treat cancer.

Abstract Understanding the impacts of the Indonesian Throughflow (ITF) on the eastward propagation of the Madden-Julian Oscillation (MJO) is crucial for accurately simulating the MJO and achieving high-skill sub-seasonal predictions. Our analyses demonstrate a significant enhancement of MJO eastward propagation due to the strong ITF. Blocking the ITF decreases the eastward sea surface temperature (SST) gradient over the tropical Indian Ocean, hindering MJO propagation across the Maritime Continent (MC). Removing the MJO circulation-induced intraseasonal variability of the ITF transport also weakens the eastward propagation of the MJO, as the MJO easterly winds enhance the ITF transport and warm the eastern tropical Indian Ocean. These experiments reveal that mean and intraseasonal variability of the ITF transport contribute to 73% and 42% of the eastward propagation of the MJO over the MC, respectively. The findings presented in this study highlight the significant role of the ITF in shaping the propagation of the MJO.

Abstract Temperature is an important limiting factor in the counter-seasonal cultivation of pepper. Currently, there are no studies on transcriptomic analysis of ‘cold stress memory’ in pepper. In this study, in order to understand the mechanism of ‘cold stress memory’ in pepper (Capsicum annuum L.), seedlings were subjected to the following treatments: normal temperature treatment (P0), the first cold treatment for 3 days (P3), the recovery temperature treatment for 3 days (R3), and another cold treatment for 3 days (RP3). The results showed that P3 plants wilted the most, RP3 the second and R3 the least. Leaf reactive oxygen species (ROS) and electrolyte leakage were the most in P3, the second in RP3 and the least in R3. In addition, RP3 had the highest accumulation of zeaxanthin, violaxanthin and β-cryptoxanthin, followed by P3, and R3 had the least. These results suggest that pepper seedlings are characterized by ‘cold stress memory’. Transcriptomics was used to analyze the key genes and transcription factors involved in the biosynthesis of zeaxanthin, violaxanthin and β-cryptoxanthin during the formation of ‘cold stress memory’. This study provides candidate genes and transcription factors for an in-depth study of the cold tolerance mechanism in pepper.

Abstract Background Entomopathogenic fungal infection-induced dysbiosis of host microbiota offers a window into understanding the complex interactions between pathogenic fungi and host symbionts. Such insights are critical for enhancing the efficacy of mycoinsecticides. However, the utilization of these interactions in pest control remains largely unexplored. Results Here, we found that infection by the host-specialist fungus Metarhizium acridum alters the composition of the symbiotic microbiota and increases the dominance of some bacterial symbionts in locusts. Meanwhile, M. acridum also effectively limits the overgrowth of the predominant bacteria. Comparative transcriptomic screening revealed that the fungus upregulates the production of MaCFEM1, an iron-binding protein, in the presence of bacteria. This protein sequesters iron, thereby limiting its availability. Functionally, overexpression of MaCFEM1 in the fungus induces iron deprivation, which significantly suppresses bacterial growth. Conversely, MaCFEM1 knockout relieves the restriction on bacterial iron availability, resulting in iron reallocation. Upon ΔMaCFEM1 infection, some host bacterial symbionts proliferate uncontrollably, turning into opportunistic pathogens and significantly accelerating host death. Conclusions This study elucidates the critical role of pathogenic fungal-dominated iron allocation in mediating the shift of host microbes from symbiosis to pathogenicity. It also highlights a unique biocontrol strategy that jointly exploits pathogenic fungi and bacterial symbionts to increase host mortality. Video Abstract

Abstract Aim To explore the topological organization alterations of functional connectomes in type 2 diabetes (T2DM) patients with and without mild cognitive impairment (MCI), and compare these with structural connectomes changes. Methods Twenty-six T2DM patients with MCI (DM-MCI), 26 without cognitive impairment (DM-NC), and 28 healthy controls were included. Diffusion tensor imaging (DTI) and resting-state functional MRI images were acquired. Networks were constructed and graph-theory based network measurements were calculated. The global network parameters and nodal efficiencies were compared across the three groups using one-way ANOVA and a false-discovery rate correction was applied for multiple comparisons. Partial correlation analyses were performed to investigate relationships between network parameters, cognitive performance and clinical variables. Results In the structural connectome, the DM-MCI group exhibited significantly decreased global efficiency (Eglob) and local efficiency (Eloc) compared to the DM-NC and control groups. In the functional connectome, the DM-MCI group exhibited increased Eloc and clustering coefficient (Cp) compared to the controls. No significant differences were found in Eglob, Eloc, or Cp between the DM-NC and the control group, both in structural and functional connectomes. Nodal efficiencies decreased in some brain regions of structural and functional networks in the DM-MCI and DM-NC groups, but increased in five regions in functional network, some of which were involved in the default-mode network. Conclusion Unlike the consistently decreased global properties and nodal efficiencies in the structural connectome of T2DM patients, increases in Eloc, Cp, and nodal efficiencies in the functional connectome may be viewed as a compensatory mechanism due to functional plasticity and reorganization. Altered nodal efficiency can hint at cognitive decrements at an early stage in T2DM patients.

Abstract Background The Global Leadership Initiative on Malnutrition criteria (GLIM) was established to build a global consensus on the diagnostic criteria for malnutrition. The study aimed to assess the prevalence of the malnutrition diagnosed by GLIM criteria for patients with hepatocellular carcinoma (HCC), and to determine the role of the reduced muscle mass defined by CT scans in the GLIM criteria. Methods This cohort research was conducted on adult cirrhotic patients with HCC. The risk of malnutrition was screened by Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. The third lumbar vertebrae (L3-SMI) were used to represent the muscle mass in GLIM criteria. The variables associated with overall mortality were assessed by multivariate Cox regression analyses. Results The incidence of malnutrition diagnosed by GLIM criteria was 49.7% (179/360) in patients with HCC. If reduced muscle mass was not included in GLIM criteria, the prevalence of malnutrition was 31.7% (114/360). GLIM-defined malnutrition (HR = 1.979, 95%CI 1.019–3.841, P = 0.044) was independently associated with overall mortality in patients with HCC. However, the GLIM-defined malnutrition (without muscle mass) was not associated with overall mortality (HR = 0.863, 95%CI 0.399–1.867, P = 0.709). Conclusions Skeletal muscle mass is an integral component of the GLIM criteria for patients with HCC. The malnutrition is common in patients with HCC, and malnourishment is associated with higher overall mortality. GLIM criteria are recommended to assess the nutritional status of hospitalized patients with HCC, which is recommended and can be used as the basis for nutritional interventions.

Abstract Background The effects of low temperatures on parasitic wasps are crucial for maintaining farmland biodiversity and enhancing biological control, especially given the implications of global warming and frequent extreme cold events. Methods We studied the effects of different low temperatures (−8 ± 1 °C, −4 ± 1 °C, 0 ± 1 °C, 4 ± 1 °C, and 8 ± 1 °C) on the mating frequency and duration of male adults of Trichopria drosophilae and the number of pupae beaten by female adults, and constructed the age–stage two-sex life table of T. drosophilae. Results This study found that male T. drosophilae adults exposed to low temperatures for 12 h significantly altered their mating behavior, peaking between 15:00 and 17:00. As the temperature dropped during the exposure, both the mating frequency of T. drosophilae and the duration of pupal beating were affected. The survival rate of female adults dropped from 39.55% at 8 °C to just 21.17% at −8 °C. Low-temperature treatment shortened the development period and lifespan for T. drosophilae adults. They developed 4.71 days faster and had a total lifespan that was 10.66 days shorter than those in the control group after being exposed to −8 °C. Furthermore, the average number of eggs laid by females at −8 °C was 4.46 less than that at 8 °C and 6.16 less than that in the control group, which laid an average of 21.55 eggs. The net reproductive rate (R 0) of T. drosophilae decreased with lower temperatures, reaching a low of 23.64 at −8 °C. Conversely, the intrinsic growth rate (r m) actually increased as temperatures dropped, with the lowest value being 0.21 at −8 °C. Conclusions The findings indicate that short-term exposure to low temperatures hampers the growth and population increase of T. drosophilae, thereby reducing their effectiveness as biological control agents. Graphical Abstract

Abstract Exploring land use/cover (LULC) change is essential for the sustainable development of ecologically fragile areas. The main objective of this study was to clarify the characteristics and differences in the spatiotemporal changes of LULC on the Loess Plateau (LP) based on the transfer matrix and land use dynamics and to quantitatively describe the impact of natural factors on LULC using a geodetector. The results indicated that the overall LULC change in the LP was characterized by a decrease in the area of cropland, grassland, and bare land, and an increase in the area of woodland and built-up land. This trend shows a clear phase-change characteristic around 2000. LULC changes were primarily affected by human activities in the southeastern agricultural region. The project of returning farmland to forest and grassland had a great impact on LULC change in the central region. Vegetation was sensitive to temperature and precipitation, and the impact of LULC change was significantly higher than that in the humid region in the northwest arid region. NDVI, PRE, and TEM were determined to be the main contributors to LULC changes in the LP. These results provide a scientific basis for the sustainable development of LP.

In July 2022, an outbreak of highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b occurred among migratory birds at Qinghai Lake in China. The virus circulated in June, and reassortants emerged after its introduction into the area. Surveillance in 2023 showed that the virus did not establish a stable presence in wild waterfowl.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

Abstract Background To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. Methods We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. Results 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: − 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. Conclusion Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection.

Abstract Controversies persist about the protective effects of vaccines against acute cardiovascular events. Using electronic medical records from hospitals and influenza vaccine administration data in Beijing, China, we studied individuals vaccinated between January 1, 2016, and December 31, 2018, who experienced at least one acute cardiovascular event within two years. A self-controlled case series design calculated the relative incidence (RI) and 95% confidence interval (CI) of acute cardiovascular events within one year after vaccination. Among 1647 participants (median age: 65 years, 38.43% female), the risk of events 29–365 days post-vaccination was 0.76 times the baseline level (RI: 0.76; 95% CI: 0.68–0.84). The protective effect was more pronounced in younger participants (P = 0.043) and those without cardiovascular history (P

Abstract Human economic activities drive the production and consumption of goods and services, contribute to the achievement of the United Nations Sustainable Development Goals (SDGs). However, the extent of economic growth’s influence on the SDGs remains unclear. To fill this knowledge gap, here, we quantified the environmental effects of economic activities and explored correlations between environmental effect and achieving SDGs. We developed six Environmental Footprint Indices, with a higher score indicating better efficiency or lower burden. Here we show that the various Environmental Footprint Indices had synergistic and trade-off effects on most SDG targets indices, but the synergistic effects prevailed. As income increased, the correlation between Environmental Footprint Indices and SDG target indices gradually strengthened. improved production efficiency and consumption changes notably advance SDGs, especially in low-income group countries. Our work provides scientific insights into the impact and prospects of environmental regulation required for achieving the SDGs by 2030.

Using Shimadzu AGS-100KN universal tensile testing machine, tensile tests were conducted on copper containing antibacterial stainless steel at 25 °C, −20 °C, −60 °C, −100 °C, and −140 °C. The fracture morphology and microstructure evolution of the material were then analyzed using various techniques including scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), X-ray diffraction (XRD), and transmission electron microscopy (TEM) techniques. The experimental findings showed that with the decrease of deformation temperature, the ultimate tensile strength(UTS) increased by about 49.7 %, the yield strength (YS) increased by about 35.5 %, and the elongation(EI) decreased by about 27.3 %, showed obvious low temperature strengthening effect. The High-angle grain boundaries (HAGBs) increased with decreasing temperature, while low-angle grain boundaries (LAGBs) decreased. The plasticity gradually decreased and the strength gradually increased, resulting in an increase in its ability to resist deformation. The number of precipitated phases gradually increased, and the size also gradually becomes larger, and the interaction between the diffusely distributed precipitated phases and dislocations led to precipitation strengthening. With the decrease of temperature, the stacking fault energy gradually decreased, the SFE was 21.26 mJ/m2 at the temperature of −140 °C. The main plastic deformation mechanism of copper-containing austenitic stainless steel in the low-temperature tensile process was transformed from deformation twins to strain-induced martensitic phase transformation.

PURPOSE: Systemic inflammation and body composition are associated with survival outcomes of cancer patients. This study aimed to examine the combined prognostic value of systemic inflammatory markers and body composition parameters in patients with locally advanced cervical cancer (LACC). METHODS: Patients who underwent concurrent chemoradiotherapy (CCRT) for LACC at a tertiary referral teaching hospital between January 2010 and January 2018 were enrolled. A predictive model was established based on systemic immune-inflammation index (SII) and computer tomography-derived visceral fat-to-muscle ratio (vFMR). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method and Cox regression models. The model performance was assessed using discrimination, calibration, and clinical usefulness. RESULTS: In total, 212 patients were enrolled. The SII and vFMR were closely related, and both independently predicted survival (P < 0.05). A predictive model was established based on the above biomarkers and included three subgroups: high-risk [both high SII (>828) and high vFMR (>1.1)], middle-risk (either high SII or high vFMR), and low-risk (neither high SII nor high vFMR). The 3-year OS (PFS) rates for low-, middle-, and high-risk patients were 90.5% (86.0%), 73.9% (58.4%), and 46.8% (36.1%), respectively (P < 0.05). This model demonstrated satisfactory predictive accuracy (area under the curve values for predicting 3-year OS and PFS were 0.704 and 0.718, respectively), good fit (Hosmer–Lemeshow tests: P > 0.05), and clinical usefulness. CONCLUSION: Systemic inflammatory markers combined with body composition parameters could independently predict the prognosis of patients with LACC, highlighting the utilization of commonly collected indicators in decision-making processes. CLINICAL SIGNIFICANCE: The SII and vFMR, as well as their composite indices, were promising prognostic factors in patients with LACC who received definitive CCRT. Future studies are needed to explore novel therapies to improve the outcomes in high-risk patients.

Abstract Background Cognitive impairment is a core symptom of schizophrenia. Metabolic abnormalities impact cognition, and although the influence of blood lipids on cognition has been documented, it remains unclear. We conducted a small cross-sectional study to investigate the relationship between blood lipids and cognition in patients with stable-phase schizophrenia. Using Olink proteomics, we explored the potential mechanisms through which blood lipids might affect cognition from an inflammatory perspective. Methods A total of 107 patients with stable-phase schizophrenia and cognitive impairment were strictly included. Comprehensive data collection included basic patient information, blood glucose, blood lipids, and body mass index. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the MATRICS Consensus Cognitive Battery (MCCB). After controlling for confounding factors, we identified differential metabolic indicators between patients with mild and severe cognitive impairment and conducted correlation and regression analyses. Furthermore, we matched two small sample groups of patients with lipid metabolism abnormalities and used Olink proteomics to analyze inflammation-related differential proteins, aiming to further explore the association between lipid metabolism abnormalities and cognition. Results The proportion of patients with severe cognitive impairment (SCI) was 34.58%. Compared to patients with mild cognitive impairment (MCI), those with SCI performed worse in the Attention/Alertness (t = 2.668, p = 0.009) and Working Memory (t = 2.496, p = 0.014) cognitive dimensions. Blood lipid metabolism indicators were correlated with cognitive function, specifically showing that higher levels of TG (r = -0.447, p

The global food crisis has intensified with climate change, and hybrid rice (Oryza sativa L.) is expected to play a crucial role in ensuring world food security. This study analyzed the parental origins and variety characteristics of 930 hybrid rice varieties bred in Sichuan Province, a typical low-light region and one of the main production areas for hybrid rice, from 2002 to 2022. The results indicate that these varieties were hybridized using 329 direct female and 539 direct male parents. Notably, the female parent Peiai 64 and the male parents Yuehesimiao and Fenghuazhan demonstrated a higher probability of breeding rice varieties with high yield and good quality. An ideal panicle type should possess more grains, a lower 1000-grain weight, a higher seed setting percentage, and greater grain density. It is recommended to increase the utilization of excellent parents in Sichuan Province, such as parents with ideal panicle type to improve resistance to climate change, particularly global dimming.

Background: Streptococcus agalactiae is a recognized pathogen that primarily affects infants and pregnant women. However, its increasingly important role in causing invasive infections among non-pregnant adults has become a significant health concern due to the severity and variety of its clinical impacts. Methods: Nonduplicate S. agalactiae clinical strains associated with clinical infections (n = 139) were isolated from non-pregnant adults in Shandong, China. Antibiotic susceptibility testing, whole-genome sequencing and genomic analyses were conducted to characterize the genome and identify resistance features of these strains. Results: The strains exhibited universal susceptibility to penicillin, ampicillin, cefotaxime, meropenem, linezolid and vancomycin. Notably, high resistance rates were observed for erythromycin (91.4%), clindamycin (89.2%), levofloxacin (84.2%), tetracycline (54.0%) and, to a lesser extent, chloramphenicol (12.9%). Serotyping revealed seven serotypes and one non-typeable strain. Serotypes Ia, Ib, III and V predominated, representing 95.7% of the strains. Nineteen sequence types were categorized into seven clonal complexes, with CC10 being the most prevalent at 48.9%. The resistance genes mreA (100%), ermB (70.5%) and tetM (46.0%) were commonly detected. All the isolates carried at least one pilus backbone determinant and one alpha-like protein gene, with the PI-1+PI-2a and the bca gene being the most frequent at 84.2% and 54.7%, respectively. Conclusions: While S. agalactiae strains in non-pregnant adults retain sensitivity to β-lactam antibiotics, the elevated resistance to erythromycin, clindamycin, levofloxacin and tetracycline is concerning. Given the growing elderly population worldwide, the burden of S. agalactiae infections is significant. Continuous surveillance of serotype distribution and antibiotic resistance patterns is imperative for targeted prevention and therapeutic strategies.

ABSTRACTBackground Pneumococcal vaccines are effective in preventing pneumococcal diseases in adults. The evaluation of the antibodies persistence to the 23-valent pneumococcal polysaccharide vaccine (PPV23) could provide evidence on PPV23 revaccination.Research design and methods Adults aged ≥ 60 years were selected and vaccinated with PPV23 in Shanghai, and followed up for 5 years with blood samples collection of a 1-year interval. The geometric mean concentrations (GMC) of the IgG against 23 pneumococcal serotypes covered by PPV23 were detected using enzyme-linked immunosorbent assay. The antibodies to 23 pneumococcal serotypes among different groups was analyzed using statistical analysis.Results Overall, 517 participants completed all six visits over a 5-year period (2013–2018). The GMC of 23 serotypes in adults aged ≥ 60 years decreased slowly after PPV23 vaccination compared to baseline pre-vaccination (P

We aimed to assess the effect of osthole on the inflammatory responses of mice suffering from primary Sjögren's syndrome (PSS). Fifty naive non‐obese diabetic (NOD/Ltj) mice were included to establish a spontaneous model of PSS and assigned into a control group, a 20 mg/kg osthole group, a 30 mg/kg osthole group, a 40 mg/kg osthole group and a 50 mg/kg osthole group in a random manner. Osthole (20, 30, 40, and 50 mg/kg, once a day) together with normal saline (every day) in an equal volume were injected into osthole treatment groups and control group, respectively. Compared with the control group, the inflammatory cells in salivary gland tissues of NOD/Ltj mice manifested gradually ameliorated infiltration, the destruction of acinar cells was relieved gradually (P

Abstract Objective To investigate the impact of vitamin A (VA), vitamin D (VD), and homocysteine (Hcy) on cardiometabolic multimorbidity (CMM). Methods This study is a cross-sectional study conducted in Ningxia Province, China. A total of 5000 participants aged 25–74 were recruited and divided into two groups based on the definition of cardiometabolic multimorbidity: the CMM group and the Non CMM group. Demographic, lifestyle, and laboratory data were collected to investigate the correlation between vitamin A, D, Hcy levels and CMM risk. The association was analyzed using multiple logistic regression and restricted cubic spline method. Results CMM incidence increased with age, being higher in females (20.05%) compared to males, Hypertension was present in 96.20% of CMM cases. Reduced VD levels correlated with an elevated CMM risk (OR = 1.799, 95% CI: 1.466–2.238), showing an inverse dose-response relationship, even after adjusting for confounders (OR = 1.553, 95% CI: 1.233–1.956). However, VA and Hcy levels were not significantly associated with CMM risk. The inverse correlation between VD status and CMM risk was more pronounced in males, obese individuals, and those with normal blood lipid profiles (P

Abstract Background Chronic diseases, such as heart disease, cancer, and diabetes, are the leading causes of death and disability. Loneliness is linked to a greater risk of chronic disease. However, the lack of loneliness may change this relationship. Methods The 4th Survey of the Aged Population in Urban and Rural China (SSAPUR) was performed. 222,179 people over 60 years old were recruited. Chronic disease was defined by self-reported tumble incidents using the fourth SSAPUR questionnaire. We found that the residuals were well normally distributed. Subsequently, we analyzed the association between each studied factor and chronic disease by univariate logistic regression analysis. Finally, we stratified the population by age, gender, and urban and rural. Results 77,448 individuals experienced loneliness, while 137,593 did not. Loneliness correlated significantly with urban-rural classification, age, and gender (P

Abstract In response to the covid-19 pandemic, the digital strategy of education has become a key pedagogical approach for higher engineering disciplines. In this complex environment, the outcome-oriented higher engineering discipline faces the challenge of educational equity in terms of curriculum design and learning outcome assessment for its online engineering practical courses. In order to solve this problem, this study develops a digital teaching assistant system to facilitate the reform of educational equity in higher engineering disciplines. The teaching and learning functions of the system aim to support the interaction between teachers and students in the teaching process and the visual display of learning outcomes, and its intelligent evaluation and analysis function is based on the multi-criterion group decision-making model of Quality Function Deployment (QFD) combined with t-test to realize the evaluation of course learning outcomes. The results show that the academic performance of this system is significantly better than that of other similar systems. The statistical results of the teacher-student satisfaction survey of the two systems show that the teacher-student interaction and multi-dimensional learning evaluation analysis report function provided by the system are the most highly recognized, and the system also has better educational equity in resource recommendation, interaction and collaboration, learning achievement display and learning achievement evaluation, etc. In addition, the system is more in line with the teaching characteristics of higher engineering disciplines, which can provide effective assistance for teachers of higher engineering disciplines to improve teaching plan and cultivate students’ disciplinary practicality, consequently creating favorable conditions for the establishment of teaching equity.

In the last 40 years, there has been a notable rise in the occurrence of diabetes within China, leading to the country now having the highest number of individuals affected by this condition globally. This prospective observational study examined the effect of different baseline relative leukocyte telomere length (RTL) and the combined effect of baseline RTL and plasma phospholipid fatty acid (PPFA) on the risk of developing diabetes. Adults from Ningxia Province who underwent baseline and follow-up surveys were included in the study. The correlation between the baseline RTL and PPFA was investigated using a multiple linear regression model. The combined effects of baseline RTL and PPFA levels on the risk of developing type 2 diabetes mellitus (T2DM) were investigated using a Cox regression model with time as the covariate. A total of 1461 study subjects were included in this study. According to the diagnostic criteria of the Chinese Diabetes Society, 141 subjects developed T2DM during the follow-up period. The baseline age was negatively correlated with RTL. After adjustment for age, C16:0, C18:1 n-9, C20:4 n-6, C20:3 n-3, and monounsaturated fatty acid (MUFA) concentrations were negatively correlated with RTL. Multiple linear regression analysis showed that C16:0 and MUFA concentrations influenced RTL. Subjects with shorter RTL at baseline had a higher risk of developing diabetes than those with longer RTL. Subjects with shorter RTL and higher C16:0 and MUFA concentrations at baseline had a higher risk of developing T2DM than those with longer RTL and lower C16:0 and MUFA concentrations. Our findings indicated that PPFA affects changes in RTL. In addition, RTL and PPFA are associated with the occurrence of T2DM.

Abstract The precise forecasting of air quality is of great significance as an integral component of early warning systems. This remains a formidable challenge owing to the limited information of emission source and the considerable uncertainties inherent in dynamic processes. To improve the accuracy of air quality forecasting, this work proposes a new spatiotemporal hybrid deep learning model based on variational mode decomposition (VMD), graph attention networks (GAT) and bi-directional long short-term memory (BiLSTM), referred to as VMD–GAT–BiLSTM, for air quality forecasting. The proposed model initially employ a VMD to decompose original PM2.5 data into a series of relatively stable sub-sequences, thus reducing the influence of unknown factors on model prediction capabilities. For each sub-sequence, a GAT is then designed to explore deep spatial relationships among different monitoring stations. Next, a BiLSTM is utilized to learn the temporal features of each decomposed sub-sequence. Finally, the forecasting results of each decomposed sub-sequence are aggregated and summed as the final air quality prediction results. Experiment results on the collected Beijing air quality dataset show that the proposed model presents superior performance to other used methods on both short-term and long-term air quality forecasting tasks.

Abstract Background Despite its known significance in plant abiotic stress responses, the role of the RAV gene family in the response of Capsicum annuum to chilling stress remains largely unexplored. Results In this study, we identified and characterized six members of the CaRAV gene subfamily in pepper plants through genome-wide analysis. Subsequently, the CaRAV subfamily was classified into four branches based on homology with Arabidopsis thaliana, each exhibiting relatively conserved domains within the branch. We discovered that light response elements accounted for the majority of CaRAVs, whereas low-temperature response elements were specific to the NGA gene subfamily. After pepper plants were subjected to chilling stress, qRT‒PCR analysis revealed that CaRAV1, CaRAV2 and CaNGA1 were significantly induced in response to chilling stress, indicating that CaRAVs play a role in the response to chilling stress. Using virus-induced gene silencing (VIGS) vectors, we targeted key members of the CaRAV gene family. Under normal growth conditions, the MDA content and SOD enzyme activity of the silenced plants were slightly greater than those of the control plants, and the REC activity was significantly greater than that of the control plants. The levels of MDA and electrolyte leakage were greater in the silenced plants after they were exposed to chilling stress, and the POD and CAT enzyme activities were significantly lower than those in the control, which was particularly evident under repeated chilling stress. In addition, the relative expression of CaPOD and CaCAT was greater in V2 plants upon repeated chilling stress, especially CaCAT was significantly greater in V2 plants than in the other two silenced plants, with 3.29 and 1.10 increases within 12 and 24 h. These findings suggest that CaRAV1 and CaNGA1 positively regulate the response to chilling stress. Conclusions Silencing of key members of the CaRAV gene family results in increased susceptibility to chilling damage and reduced antioxidant enzyme activity in plants, particularly under repeated chilling stress. This study provides valuable information for understanding the classification and putative functions of RAV transcription factors in pepper plants.

Abstract Background Acinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province. Results Non-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained bla ADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite. Conclusions This study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii.

Abstract Background Migraine is one of the most common diseases worldwide while current treatment options are not ideal. New therapeutic classes of migraine, the calcitonin gene-related peptide (CGRP) antagonists, have been developed and shown considerable effectiveness and safety. The present study aimed to systematically evaluate the efficacy and safety of atogepant, a CGRP antagonist, for migraine prophylaxis from the results of randomized controlled trials (RCTs). Methods The Cochrane Library, Embase, PubMed and https://www.clinicaltrials.gov/ were searched for RCTs that compared atogepant with placebo for migraine prophylaxis from inception of the databases to Feb 1, 2024. Outcome data involving efficacy and safety were combined and analyzed using Review Manager Software version 5.3 (RevMan 5.3). For each outcome, risk ratios (RRs) or standardized mean difference (SMD) were calculated. Results 4 RCTs with a total of 2813 subjects met our inclusion criteria. The overall effect estimate showed that atogepant was significantly superior to placebo in terms of the reduction of monthly migraine (SMD − 0.40, 95% CI -0.46 to -0.34) or headache (SMD − 0.39, 95% CI -0.46 to -0.33) days, the reduction of acute medication use days (SMD − 0.45, 95% CI -0.51 to -0.39) and 50% responder rate (RR 1.66, 95% CI 1.46 to 1.89), while no dose-related improvements were found between different dosage groups. For the safety, significant number of patients experienced treatment-emergent adverse events (TEAEs) with atogepant than with placebo (RR 1.10, 95% CI 1.02–1.21) while there was no obvious difference between the five dosage groups. Most TEAEs involved constipation (RR 2.55, 95% CI 1.91–3.41), nausea (RR 2.19, 95% CI 1.67–2.87) and urinary tract infection (RR 1.49, 95% CI 1.05–2.11). In addition, a high dosage of atogepant may also increase the risk of treatment-related TEAEs (RR 1.64, 95% CI 1.02–2.63) and fatigue (RR 3.07, 95% CI 1.13–8.35). Conclusions This meta-analysis suggests that atogepant is effective and tolerable for migraine prophylaxis including episodic or chronic migraine compared with placebo. It is critical to weigh the benefits of different doses against the risk of adverse events in clinical application of atogepant. Longer and multi-dose trials with larger sample sizes are required to verify the current findings.

Abstract Pu'er crude tea (PCT), the initial raw material for making Pu'er tea, is favored because of unique flavor and health effects. Emotional response is helpful to explain consumers’ choice of different flavors of tea. This study aims to clarify the key floral volatiles of PCT and their emotional impact on people. Twenty‐nine compounds were identified as the key volatiles from 237 volatiles, which formed the flowery aroma of PCT. Linalool, geraniol, nonanal, and methyl salicylate were more abundant in the PCT, they evoked the top five emotions (mild, wild, aggressive, tame, bored). Methyl salicylate contributed most to the wild emotion in the two mixed samples (B10 and B14), and it may contribute positively to the health effects of tea, such as refreshing and anti‐inflammatory. This study provided a preliminary research idea for exploring the relationship between tea aroma and human emotions and its potential role in human health.

Abstract Objective Relational job characteristics include perceived social worth and perceived social influence. Good relational job characteristics mean that nurses have high prosocial behavior. The purpose of this study was to explore the potential profile of nurses’ relational job characteristics, influencing factors and their differences in turnover intention and subjective well-being, thus finding the most suitable clinical relationship job characteristics. Methods A cross-sectional survey was conducted among 1013 clinical nurses using the general demographic data questionnaire, Relational Job Characteristics scale, Turnover Intention Questionnaire and Campbell index of well-being. A latent profile analysis was performed to explore relational job characteristics latent profiles. Multinomial logistic regression analysis was conducted to examine the predictors of profile membership, and a one-way analysis of variance was applied to compare the turnover intention and subjective well-being in each latent profile. Results Five latent profiles were identified and labeled ‘High prosocial job characteristics’ profile (20.7%), ‘Moderate prosocial job characteristics’ profile (41.7%), ‘High social worth-low social impact perceived’ profile (6.3%), ‘Low social worth‐high social impact perceived’ profile (18.8%) and ‘Low prosocial job characteristics’ profile (12.5%). Factors affecting the different types of nurse relationship job characteristics include age, marital status, hospital department, nursing years, professional title and hospital position. Among them, chief nurse, nurses with more than 20 years of nursing experience and obstetrics and gynecology nurses were more likely to be ‘high prosocial job characteristics’ profile. The turnover intention of nurses in ‘high prosocial job characteristics’ profile was significantly lower than that of other profiles, and their subjective well-being was significantly higher than that of other profiles. Conclusion Improving nurses’ perception of social worth and social impact on clinical work can improve nurses’ prosocial behavior and subjective well-being, and reduce their turnover intention. Nursing managers or policy makers can formulate targeted intervention measures according to the influencing factors of potential profiles.

Abstract The Mu Us Sandy Land is a region characterized by wind-blown sand and soil erosion in northern China. To enhance the soil quality of this area, various organic materials were incorporated into the mixed soil at a volume ratio of 1:2 for feldspathic sandstone to sand. Culture was conducted in the field and under constant temperature conditions in laboratory culture chambers. Four treatments were established in the experiment, each calculated based on weight ratio and controlled (with no organic material added, CK); single application of straw (5% straw, P1); single application of biochar (5% biochar, P2); combined application of biochar and straw (5% biochar + 5% straw, P3). After 90 days of culture, soil samples were collected for analysis of various indicators such as soil aggregate particle size distribution, water stability of soil aggregates, mean weight diameter, mean geometric diameter, and fractal dimension using dry sieving and wet sieving methods. The objective is to establish a scientific basis and provide technical support for addressing the challenges associated with compound soil and implementing rational fertilization measures. The research results indicate that: (1) The quantity of aggregates > 0.25 mm under different treatments follows the order CK 0.25 (x) of compound soil, with a correlation coefficient of up to 0.9851. In conclusion, the incorporation of organic materials can effectively enhance the proportion of macroaggregates in compound soil consisting of Feldspathic sandstone and sand, thereby improving soil stability and erosion resistance. The optimal outcome is achieved through the combined application of biochar and straw. Indoor culture proves to be more effective than field culture, while wet sieving accurately reflects the structural characteristics of compound soil under both dry and wet sieving treatments.

Abstract To explore the related factors of turnover intention in clinical research coordinators (CRCs) and assess the mediating effects of professional identity on the association between job burnout and turnover intention. In China, CRC has become increasingly common among clinical trial teams in recent years. However, limited published research focused on the status of turnover intention in CRCs. We invited all the 220 CRCs currently working at Hunan Cancer Hospital located in Changsha city in the central south of China from March to June 2018. Participants were asked to complete structured questionnaires regarding basic demographic information, job burnout, professional identity and turnover intention. A total of 202 participants were included in this study, with a response rate of 91.82%. The main reason for turnover intention among CRCs was human resources, followed by communications, management and material resources (per item score in each dimension: 2.14 vs. 2.43 vs. 2.65 vs. 2.83). All the correlations among job burnout, professional identity and turnover intention were statistically significant, with coefficients ranging from −0.197 to 0.615. Multiple liner regression analysis showed that older age, longer workhours per week, and lower level of professional identity were associated with the prevalence of turnover intention among CRCs. Besides, the association between job burnout and turnover intention was fully mediated by professional identity. This study revealed the status and causes of turnover intention among Chinese CRCs. Effective measures on decreasing working time and improving professional identity should be taken in order to reduce CRCs’ turnover intention.

Abstract Background Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. Methods In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. Results Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency. Conclusions In summary, our findings demonstrate that the H19/let-7 g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.

Abstract The COVID-19 lockdown has forced young children to spend more time on media and significantly impacted their mothers’ mental health. This study explored how mothers’ individual distress influences children’s problematic media use during the Shanghai citywide lockdown caused by COVID-19. Data were collected from 1889 Chinese mothers (M age = 34.69 years, SD = 3.94 years) with preschoolers aged 3–6 years (M age = 4.38 years, SD = 1.06 years; 49.0% boys) via an online survey. The statistical analyses relied on SPSS Statistics version 26.0 and macro-program PROCESS 3.3. to investigate the associations and mediation analysis among all the study variables. The results indicated a positive association between maternal distress and children’s problematic media use, mediated by parenting stress and maladaptive parenting. Specifically, the serial mediation analysis revealed that high levels of maternal distress exacerbate parenting stress, which in turn leads to maladaptive parenting practices. These maladaptive practices subsequently increase problematic media use in preschool children. The findings highlighted that parents need to enhance their ability to manage risk and promote mental health during periods of significant stress and routine disruption to reduce children’s problematic media use.

Abstract Background Metastasis is the leading cause of mortality in patients with colorectal cancer (CRC) and angiogenesis is a crucial factor in tumor invasion and metastasis. Long noncoding RNAs (lncRNAs) play regulatory functions in various biological processes in tumor cells, however, the roles of lncRNAs in CRC-associated angiogenesis remain to be elucidated in CRC, as do the underlying mechanisms. Methods We used bioinformatics to screen differentially expressed lncRNAs from TCGA database. LOC101928222 expression was assessed by qRT-PCR. The impact of LOC101928222 in CRC tumor development was assessed both in vitro and in vivo. The regulatory mechanisms of LOC101928222 in CRC were investigated by cellular fractionation, RNA-sequencing, mass spectrometric, RNA pull-down, RNA immunoprecipitation, RNA stability, and gene-specific m6A assays. Results LOC101928222 expression was upregulated in CRC and was correlated with a worse outcome. Moreover, LOC101928222 was shown to promote migration, invasion, and angiogenesis in CRC. Mechanistically, LOC101928222 synergized with IGF2BP1 to stabilize HMGCS2 mRNA through an m6A-dependent pathway, leading to increased cholesterol synthesis and, ultimately, the promotion of CRC development. Conclusions In summary, these findings demonstrate a novel, LOC101928222-based mechanism involved in the regulation of cholesterol synthesis and the metastatic potential of CRC. The LOC101928222-HMGCS2-cholesterol synthesis pathway may be an effective target for diagnosing and managing CRC metastasis.

The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.

Abstract Objective Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function. Methods In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis. Results After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma. Conclusions Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.

Abstract Effects of short-term exposure to ambient air pollution on systemic immunological and inflammatory biomarkers in rural population have not been adequately characterized. From May to July 2021, 5816 participants in rural villages of northern Henan Province, China, participated in this cross-sectional study. Blood biomarkers of systemic inflammation were determined including peripheral white blood cells (WBC), eosinophils (EOS), basophils (BAS), monocytes (MON), lymphocytes (LYM), neutrophils (NEU), neutrophil-lymphocyte ratio (NLR), and serum high-sensitivity C-reactive protein (hs-CRP). The concentrations of ambient fine particulate matter (PM2.5), PM10, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were assessed up to 7 days prior to the blood draw. A generalized linear model was used to analyze the associations between air pollution exposure and the above-mentioned blood biomarkers. Significantly positive associations were revealed between PM2.5, CO and WBC; CO, O3 and LYM; PM2.5, PM10, SO2, CO and NEU; PM2.5, PM10, SO2, CO and NLR; PM2.5, PM10, SO2, NO2, CO, O3 and hs-CRP. Meanwhile, negative associations were found between SO2 and WBC; PM2.5, PM10, NO2, CO, or O3 and EOS; PM2.5, SO2, or CO and BAS; SO2, NO2 or O3 and MON; PM2.5, PM10, SO2, or NO2 and LYM. Moreover, men, individuals with normal body mass index (BMI), current smokers, and those older than 60 years were found vulnerable to air pollution effects. Taken together, short-term exposure to air pollution was associated with systemic inflammatory responses, providing insight into the potential mechanisms for air pollution-induced detrimental systemic effects in rural residents.

The current study analyzed the chromosomal karyotype of Quasipaa spinosa David, 1875 from Hunan Province, China. The karyotype, C-banding, BrdU-banding pattern were characterized using direct preparation of bone-marrow cells and hemocyte cultures. The findings indicated that Q. spinosa was a diploid species (2n = 26) that lacked heteromorphic chromosomes and secondary constrictions. C-banding analysis revealed an abundance of positive signals in the centromere regions, while the BrdU-banding pattern showed three phases in both male and female, occurring consistently and in chronological sequence during S-phase. Notably, there was no asynchronous replication in the late phase. This study enhanced our understanding of the karyotypic structure of Q. spinosa by conventional cytogenetic techniques, thus providing essential scientific insights into the cytogenetics of Q. spinosa.

Abstract Background Patients receiving PD-(L)1 inhibitors frequently encounter unusual side effects known as immune-related adverse events (irAEs). However, the correlation of irAEs development with clinical response in small cell lung cancer (SCLC) is unknown. Method This retrospective study enrolled 244 stage IV SCLC patients who receiving PD-(L)1 inhibitors from 3 cancer centers. The correlation of irAEs with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results 140 in 244 (57%) patients experienced irAEs, with 122 (87.1%) experiencing one and 18 (12.9%) experiencing two or more. Compared to patient without irAEs, those developing irAEs had higher ORR (73.6% vs. 52.9%, P

Abstract As urban areas expand globally, human activities are leading to a sustained increase in non-methane volatile organic compound (NMVOC) emissions, escalating both environmental and health-related concerns. Given their diverse origins, estimating anthropogenic NMVOC emissions levels from global urban areas remains challenging. Here, we integrate TROPOspheric Monitoring Instrument (TROPOMI) formaldehyde (HCHO) column data, Visible Infrared Imaging Radiometer Suite (VIIRS) nighttime light (NTL) radiance data, and the Emission Database for Global Atmospheric Research (EDGAR) to develop a method for estimating global anthropogenic NMVOC emissions. Furthermore, we construct a linear model to analyze the relationship between urbanization and anthropogenic NMVOC emissions. Our research reveals that meticulously filtered TROPOMI HCHO columns have a high Pearson correlation coefficient (r = 0.91) with anthropogenic NMVOC emissions, indicating its reliability as an indicator reflecting the levels of anthropogenic NMVOC emissions. We establish linear models at various scales, including global, continental, and national, linking HCHO columns (as indicators of anthropogenic NMVOC emissions) and NTL radiance (as an indicator of urbanization). The global-scale linear model exhibits an r of 0.81, with a slope of 0.42 × 1015 molec. cm−2 nanoWatts−1 cm2 sr and an intercept of 9.26 × 1015 molec. cm−2. This linear model reflects a positive correlation between urbanization and anthropogenic NMVOC emissions, also serving as a tool for estimating the levels of anthropogenic NMVOC emissions in urban areas. This study offers valuable insights for real-time monitoring of extensive anthropogenic NMVOC emissions.

Abstract Background Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils. Methods Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type mice. Megakaryocyte differentiation was investigated using lineage-negative bone marrow cells upon in vitro incubation with TPO/IL-1β. Cytokine concentrations in serum of mice were determined by Mouse Cytokine Array. IL-1α expression in various hematopoietic cell populations was determined by intracellular FACS analysis. RNA-seq to analyse gene expression of inflammatory cytokines was performed in isolated neutrophils from JAK2-V617F and CALR-mutated mice and patients. Bioenergetics of neutrophils were recorded on a Seahorse extracellular flux analyzer. Cell motility of neutrophils was monitored in vitro (time lapse microscopy), and in vivo (two-photon microscopy) upon creating an inflammatory environment. Cell adhesion to integrins, E-selectin and P-selection was investigated in-vitro. Statistical analysis was carried out using GraphPad Prism. Data are shown as mean ± SEM. Unpaired, two-tailed t-tests were applied. Results Strikingly, neutrophil-specific expression of JAK2-V617F, but not CALRdel, was sufficient to induce pro-inflammatory cytokines including IL-1 in serum of mice. RNA-seq analysis in neutrophils from JAK2-V617F mice and patients revealed a distinct inflammatory chemokine signature which was not expressed in CALR-mutant neutrophils. In addition, IL-1 response genes were significantly enriched in neutrophils of JAK2-V617F patients as compared to CALR-mutant patients. Thus, JAK2-V617F positive neutrophils, but not CALR-mutant neutrophils, are pathogenic drivers of inflammation in MPN. In line with this, expression of JAK2-V617F or CALRdel elicited a significant difference in the metabolic phenotype of neutrophils, suggesting a stronger inflammatory activity of JAK2-V617F cells. Furthermore, JAK2-V617F, but not CALRdel, induced a VLA4 integrin-mediated adhesive phenotype in neutrophils. This resulted in reduced neutrophil migration in vitro and in an inflamed vessel. This mechanism may contribute to the increased thrombotic risk of JAK2-V617F patients compared to CALR-mutant individuals. Conclusions Taken together, our findings highlight genotype-specific differences in MPN-neutrophils that have implications for the differential pathophysiology of JAK2-V617F versus CALR-mutant disease.

Upon chemotherapy, excessive reactive oxygen species (ROS) often lead to the production of massive lipid peroxides in cancer cells and induce cell death, namely ferroptosis. The elimination of ROS is pivotal for tumor cells to escape from ferroptosis and acquire drug resistance. Nevertheless, the precise functions of long non-coding RNAs (lncRNAs) in ROS metabolism and tumor drug-resistance remain elusive. In this study, we identify LncRNA-HMG as a chemoresistance-related lncRNA in colorectal cancer (CRC) by high-throughput screening. Abnormally high expression of LncRNA-HMG predicts poorer prognosis in CRC patients. Concurrently, we found that LncRNA-HMG protects CRC cells from ferroptosis upon chemotherapy, thus enhancing drug resistance of CRC cells. LncRNA-HMG binds to p53 and facilitates MDM2-mediated degradation of p53. Decreased p53 induces upregulation of SLC7A11 and VKORC1L1, which contribute to increase the supply of reducing agents and eliminate excessive ROS. Consequently, CRC cells escape from ferroptosis and acquire chemoresistance. Importantly, inhibition of LncRNA-HMG by anti-sense oligo (ASO) dramatically sensitizes CRC cells to chemotherapy in patient-derived xenograft (PDX) model. LncRNA-HMG is also a transcriptional target of β-catenin/TCF and activated Wnt signals trigger the marked upregulation of LncRNA-HMG. Collectively, these findings demonstrate that LncRNA-HMG promotes CRC chemoresistance and might be a prognostic or therapeutic target for CRC.

BackgroundWe found that a subset of patients with monoclonal gammopathy exhibited hypercalcemia without apparent causes or clinical manifestations In a cohort of 289 monoclonal gammopathy patients, 2.4% presented with such atypical hypercalcemia, with one notable case exhibiting normal ionized calcium levels, suggesting the presence of pseudohypercalcemia.ObjectiveThe aim of this study is to elucidate the factors contributing to pseudohypercalcemia in monoclonal gammopathy and to develop a novel globulin-corrected calcium formula for clinical application.MethodsThis observational study enrolled 110 monoclonal gammopathy patients from our center. An additional 33 patients were recruited to validate the newly proposed formula. Univariate analysis identified potential risk factors. And multivariate logistic regression identified definitive influential factors. The determined influential factors were utilized to develop a formula by multiple linear regression, which was validated by a paired t-test and the Youden index.ResultsThis study found that globulin was a risk factor for pseudohypercalcemia. It revealed that pseudohypercalcemia should be considered in patients with globulin levels ≥61 g/L (P=0.014). Both albumin and globulin were confirmed as independent factors associated with bound calcium. Given that, we developed a formula to correct ionized calcium levels, which was consistent with ionized calcium tested by blood gas analysis. The diagnostic accuracy of the new formula (Youden index is 0.906) is better than the traditional formula (Youden index is 0.906). Interestingly, all monoclonal immunoglobulin types, except for light chains, showed an equal propensity to develop pseudohypercalcemia (P=0.306). It also showed a linear correlation between IgA, IgG, and IgM and bound calcium.ConclusionThis study confirmed that elevated globulin affects serum total calcium and offered the threshold of globulin ≥ 61 g/L in the differential diagnosis of peudohypercalcemia from hypercalcemia. The new formula based on albumin and globulin was developed, which was verified to be better than the traditional formula for correctly diagnosing hypercalcemia. In addition, we found that neither light chains nor heavy chains of monoclonal immunoglobulin alone can result in pseudohypercalcemia.

ABSTRACT Objective Chronic kidney disease (CKD) is increasingly recognized as a risk factor for alterations in brain function. However, detecting early‐stage symptoms and structural changes remains challenging, potentially leading to delayed treatment. In our study, we aimed to investigate spontaneous brain activity changes in CKD patients using resting‐state functional magnetic resonance imaging (fMRI). Additionally, we explored the correlation between common biomarkers reflecting CKD severity and brain activity. Methods We recruited a cohort of 22 non–dialysis‐dependent CKD patients and 22 controls for resting‐state fMRI scans. Amplitude of low‐frequency fluctuations (ALFFs) and regional homogeneity (ReHo) were calculated to evaluate brain activity. Regression analysis was conducted to explore the correlations between biomarkers reflecting the severity of CKD and brain activity. Results CKD patients exhibited reduced z‐scored ALFF (zALFF) and mean ALFF (mALFF) in the bilateral putamen, right caudate nucleus, left anterior cingulate, and right precuneus. Changes in bilateral putamen were also found in smCohe‐ReHo and szCohe‐ReHo analyses. Urine albumin‐to‐creatinine ratio (UACR), urine protein‐to‐creatinine ratio (UPCR), and serum albumin levels were associated with attenuated putamen activity. Conclusion Non–dialysis‐dependent CKD patients had changes in zALFF, mALFF, smCohe‐ReHo, and szCohe‐ReHo values in specific brain regions, especially bilateral putamen. UACR, UPCR, and serum albumin levels are associated with putamen activity attenuation in rs‐fMRI.

ABSTRACT Aim This cross‐sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near‐infrared spectroscopy (fNIRS). Methods Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. Results Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale‐24 (HAMD‐24). Conclusions Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

The composition and size distribution of particles in the ocean control their optical (scattering and absorption) properties, as well as a range of biogeochemical and ecological processes. Therefore, they provide important information about the pelagic ocean ecosystem’s structure and functioning, which can be used to assess primary production, particle sinking, and carbon sequestration. Due to its harsh environment and remoteness, the particulate bio-optical properties of the Southern Ocean (SO) remain poorly observed and understood. Here, we combined field measurements from hydrographic casts from two research voyages and from autonomous profiling floats (BGC-Argo) to examine particulate bio-optical properties and relationships among several ecologically and optically important variables, namely the phytoplankton chlorophyll a concentration (Chl), the particulate absorption coefficient (ap), the particulate backscattering coefficient (bbp), and the particulate organic carbon (POC) concentration. In the clearest waters of the SO (Chl < 0.2 mg m−3), we found a significant contribution to absorption by non-algal particles (NAP) at 442 nm, which was up to 10 times greater than the absorption by phytoplankton. This makes the particulate bio-optical properties there remarkably different from typical oceanic case 1 water. A matchup analysis confirms the impact of this larger NAP absorption on the retrieval of Chl from satellite ocean colour observations. For waters with Chl > 0.2 mg m−3, no significant differences are observed between the SO and temperate waters. Our findings also demonstrate consistency in predicting phytoplankton carbon from either Chl or bbp, suggesting that both methods are applicable in the SO.

BackgroundEpidemiological and observational studies demonstrate a comorbid relationship between hypothyroidism and atherosclerotic cardiovascular disease (ASCVD). The nature and direction of this causal relationship, however, remain unclear.ObjectiveThis study aims to elucidate the causal relationship between hypothyroidism and ASCVD using a bidirectional Mendelian randomization approach.MethodSingle nucleotide polymorphisms (SNPs) associated with hypothyroidism were identified and selected as genetic instrumental variables from aggregated data of genome-wide association studies (GWAS). The outcome of interest, ASCVD, included seven conditions: coronary artery disease (CAD), angina pectoris (AP), myocardial infarction (MI), ischemic stroke (IS), and subtypes IS-large artery atherosclerosis (IS-LAA), IS-small vessels (IS-SV), and peripheral artery disease (PAD). MR analysis employed multiple methods—chiefly inverse variance weighting (IVW), along with MR Egger, weighted median, and weighted mode—to assess causality. Cochrane's Q test was utilized to evaluate heterogeneity in the MR findings. Causal association reliability was assessed using the MR-Egger intercept, MR-PRESSO tests, and leave-one-out analysis. Reverse MR analysis ensued if forward MR identified a positive exposure-outcome association. Moreover, the DAVID database facilitated GO functional and KEGG pathway enrichment analyses of neighboring genes to instrumental variables, exploring potential disease mechanisms.ResultGWAS pooled data yielded 122 SNPs as potential instrumental variables for hypothyroidism. Forward MR analysis, using the IVW method, indicated hypothyroidism as a risk factor for CAD (OR = 2.34, 95% CI = 1.39–3.94, P = 0.001), AP (OR = 2.01, 95% CI = 1.28–3.16, P = 0.002), MI (OR = 1.02, 95% CI = 1.01–1.04, P = 0.004), and IS-SV (OR = 6.92, 95% CI = 2.45–19.55, P