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Objective: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive cancer. Although our previous study classified primary TNBC into four subtypes, comprehensive longitudinal investigations are lacking. Methods: We assembled a large-scale, real-world cohort comprised of 880 TNBC patients [465 early-stage TNBC (eTNBC) and 415 metastatic TNBC (mTNBC) patients] who were treated at Fudan University Shanghai Cancer Center. The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort. Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes. Results: The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1% (47/465). The median overall survival (OS) in the mTNBC cohort was 27.2 months [95% confidence interval (CI), 24.4–30.2 months], which indicated a poor prognosis. The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed. Consistent molecular subtypes were maintained in 77.5% of the patients throughout disease progression with the mesenchymal-like (MES) subtype demonstrating a tendency for subtype transition and brain metastasis. Additionally, a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial. Conclusions: Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression. However, we emphasize the major importance of repeat pathologic confirmation of the MES subtype.

Abstract Background Older adults with hearing impairments are vulnerable to cognitive impairment. Although previous reports suggest a correlation between widowhood and cognitive impairment, further investigation is needed to elucidate the effect of widowhood on cognitive function and the moderating effects of social support and participation on widowhood-related cognitive impairment in this vulnerable demographic. Methods The study’s data were sourced from the nationally representative Chinese Longitudinal Healthy Longevity Survey (CLHLS) for the years 2011, 2014, and 2018. Multiple linear regression was used to analyze the association between widowhood and cognitive function among older adults. Multivariate logistic regression examined the effect of widowhood on the likelihood of experiencing various levels of cognitive impairment in older adults with hearing impairments. A moderating effect model explored the roles of social support and participation in mitigating widowhood-related cognitive impairment. Results The cognitive function of older adults with hearing impairment was found to be lower than that of those without hearing impairment. Widowhood was significantly negatively correlated with Mini-Mental State Examination (MMSE) scores in older adults, both with (Coef. = -0.898) and without (Coef.: = -0.680) hearing impairments. A stronger association was observed between widowhood and declining cognitive function among older adults with hearing impairment. Specifically, widowhood may be more likely to significantly increase the likelihood of moderate and severe cognitive impairment (RRR = 1.326, 1.538) among older adults with hearing impairments. Social support and social participation significantly moderated the cognitive impairment associated with widowhood among hearing-impaired older adults. These forms of support and engagement are buffers against the risk of widowhood-related cognitive impairment among this demographic. Conclusions Our findings indicate that widowhood is significantly associated with cognitive impairment in older adults with hearing impairment. Social support and participation help mitigate this risk. Strategies should prioritize early screening, specialized cognitive rehabilitation, comprehensive care, and enhancing social support and participation to maintain cognitive health in this vulnerable population following widowhood.

Abstract Background F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). Methods This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. Results The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. Conclusions A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. Trial registration ClinicalTrials.gov: NCT04174599, on 22/11/2019.

The mechanism of phenol degradation by micro-electrolytic systems can be fully understood by evaluating the oxidation of active substances from the two aspects of phenol bond-breaking and mineralization, and the direction of promoting the generation of active substances is pointed out. In this article, the effects of H2O2, O2-•, ·OH and 1O2 in the degradation of phenol were analyzed using phenol and chemical oxygen demand (COD) removal rates as judgment indicators, respectively. And the addition of C6O8H6 to the micro-electrolysis system was adopted to promote the generation of active substances. The experimental results showed that the active substances which played a dominant effect in the process of phenol bond-breaking and mineralization were changed. While 1O2 is dominant in the bond-breaking of phenol, •OH is dominant in the mineralization of phenol. After adding C6O8H6 (1 mmol/L), the removal rates of phenol and COD were increased by 7.35 and 4.85%, respectively. This was attributed to the autoxidation reaction of C6O8H6 and the continuous supply of H+ while reducing Fe3+ to Fe2+. Additionally, the C6O8H6 regulated the reaction pathway to improve the utilization of H2O2. This study provides a new perspective for the understanding of active substances in micro-electrolysis systems. HIGHLIGHTS The main active substances in the bond-breaking and mineralization are different.; is the main active substance in the phenol bond-breaking process.; •OH is the main active substance in the phenol mineralization process.; C6O8H6 can promote the formation of active substances in the system.; C6O8H6 can promote the Fe2+/Fe3+ cycle and improve the utilization of •OH.;

Abstract Background Given the rapid population aging in China, achieving universal health coverage (UHC) presents a primary challenge in addressing unmet healthcare needs and associated inequalities among middle-aged and older adults. Several studies have focused on healthcare utilization and its inequalities, but little attention has been paid to the inequality in unmet healthcare needs. This study aimed to analyze the inequalities in unmet the healthcare needs of middle-aged and older adults in eastern China during the progression toward UHC. Methods Data were obtained from the fourth, fifth, and sixth National Health Service Survey (NHSS) of Jiangsu Province, located in eastern China, during the years 2008, 2013, and 2018, respectively. Logistic regression models were used to assess the associated factors of unmet healthcare needs. The inequality was measured according to the concentration index (CI) and its decomposition. Results In this study, we found that 12.86%, 2.22%, and 48.89% of middle-aged and older adults reported unmet needs for outpatient and inpatient services and physical examinations, respectively. The prevalence of unmet outpatient needs increased from 2008 to 2018, while the prevalence of unmet inpatient services was lower but maintained. The prevalence of unmet needs for physical examinations among middle-aged and older adults markedly decreased since 2008. Rural areas had a higher prevalence of unmet needs for inpatient services and physical examinations than urban areas. Unmet healthcare needs were more prevalent among the poor. The pro-poor inequalities of unmet healthcare needs have been mitigated during the progression toward UHC; however, they remain predominant among rural middle-aged and older adults for outpatient and inpatient services. Socioeconomic factors significantly influenced unmet healthcare needs and contributed to their inequalities. Conclusions The findings characterize the prevalence and inequality of unmet healthcare need among middle-aged and older adults in eastern China during the progression toward UHC. Policy interventions should be actively advocated to effectively mitigate the unmet healthcare needs and address the associated inequalities.

Abstract Background Levels of self-management behaviors (SMB) and quality of life (QoL) are suboptimal in Chinese adults with type 2 diabetes (T2D), especially in rural China. Integrated health management within a county medical consortium, featuring multi-level teams of doctors, nurses, and other professionals offering follow-up services such as check-ups, assessments, treatment, and health education, is promising in improving this. This study aimed to assess the effect of integrated health management within a county medical consortium on the SMB and QoL of rural T2D patients in China. Methods Based on a survey conducted on the county medical consortium in Eastern China, this study initially employed propensity score matching (PSM), a nonparametric technique, to precisely estimate the average treatment effect on the treated (ATT) of integrated health management on SMB and QoL in rural T2D patients. Subsequently, quantile regression was also performed to estimate the relationship between the implementation of integrated health management, sociodemographic factors, follow-up services (offered during integrated health management) and both SMB and QoL. Results The ATT values for SMB and QoL, representing the net effect of integrated health management within a county medical consortium on SMB and QoL, were significantly positive. They ranged from 4.34 to 4.67 for SMB and from 0.89 to 1.06 for QoL, respectively, based on the four different PSM modalities. The results of quantile regression also revealed a statistically significant positive association between the implementation of integrated health management and both SMB (coef. = 4.15) and QoL (coef. = 1.54). These findings suggest that integrated health management within a county medical consortium can effectively improve SMB and QoL in rural T2D patients. Furthermore, frequency of follow-up service and health behavior guidance were positively associated with SMB and QoL. Conversely, on-call follow-up services, medication guidance and follow-up services at medical institutions were negatively correlated with SMB or QoL. Conclusions The study highlights the effectiveness of integrated health management within a county medical consortium in improving SMB and QoL among individuals with T2D in rural China. The findings offer invaluable insights for the advancement of chronic disease management in rural areas of developing countries.

Abstract Background Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). Results Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. Conclusion This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars.

Abstract Background The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). Results Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. Conclusions Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

Numerous studies have explored the relationship between pharmacological treatment regimens and the quality of life (QoL) of type 2 diabetes (T2D) patients. However, there is a dearth of comparative studies focusing on the QoL among rural T2D patients in China across 3 distinct pharmacological treatments: oral antidiabetic drugs (OADs), insulin therapy, and a combination of OADs and insulin. Additionally, the specific correlation between these treatment regimens and distinct dimensions of QoL remains unclear, necessitating further investigation. Data from a survey of rural T2D patients in eastern China were analyzed to calculate QoL scores for different treatment groups. Multivariate linear regression was then used to assess variations in overall QoL and specific dimensions among patients on OADs, insulin, and combined therapy. OADs were most commonly used (70.36%), followed by combined (19.47%) and insulin therapy (10.17%). Patients on OADs reported the highest overall QoL, with reduced physical discomfort, improved psychological well-being, enhanced treatment satisfaction, and fewer medication side effects. Conversely, those on combined therapy had the lowest overall QoL, primarily due to increased physical discomfort. Insulin users had moderately positive overall QoL but lower psychological well-being and treatment satisfaction, along with more adverse reactions. Disparities in QoL and its dimensions exist among rural T2D patients based on treatment regimens. Healthcare providers should prioritize support systems and interventions to help patients manage side effects of insulin and combined therapy, thereby improving their QoL.

BackgroundPatients with type 2 diabetes (T2D) in rural China frequently exhibit inadequate diabetes self-management (DSM) and a reduced quality of life (QoL). Social support and self-efficacy are known to influence DSM and QoL. However, the pathways through which social support and self-efficacy impact DSM and QoL among patients with T2D in rural China has yet to be fully elucidated. ObjectiveThis study offers a foundation for developing policies in rural chronic disease management, thereby, contributing to the improvement of T2D prevention and control in China and other transitional countries. MethodsThis study used a cross-sectional design, collecting data from a survey conducted between May and July 2021 on DSM and QoL among rural patients diagnosed with T2D in 2 townships in East China. All patients with T2D were enrolled through cluster sampling from the township health center database, and a questionnaire survey was administered by investigators. Structural equation modeling and multiple regression analyses were used to explore the pathways through which social support influences DSM and QoL, as well as the mediating role of self-efficacy. ResultsIt was found that the DSM score (mean 37.42, SD 7.70) was less than half of the maximum theoretical score. The QoL score (mean 48.92, SD 8.88) accounted for 36% of the maximum theoretical score. Social support directly and positively affected the DSM and QoL of Chinese rural patients with T2D (P

ABSTRACT Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach. This study aims to screen for potential phenol-degrading bacteria and to verify the removal capacities of a selected strain in a bioaugmentation experiment at the greenhouse level using Brassica chinensis L. (Chinese cabbage) as the model plant and phenol-contaminated soil. In parallel, pot experiments were conducted using a collaborative approach based on this model system. We found that Myroides xuanwuensis strain H13 showed a high degradation capability, with a 97.67% efficiency in degrading 100 mg/L phenol. Under shaking flask conditions, H13 facilitated the solubilization of tricalcium phosphate and potassium feldspar powder. Pot experiments suggested a phenol removal percentage of 89.22% and enhanced availability of soil phosphorus and potassium for plants with H13 inoculation. In this case, the abundance of soil microbes and the activity of soil enzymes significantly increased as well. Furthermore, both photosynthesis and the antioxidant system in Chinese cabbage were enhanced following H13 inoculation, resulting in its increased yield and quality. Partial least squares path modeling revealed that H13 can primarily affect plant root growth, with a secondary impact on photosynthesis. These findings highlight the potential of biodegradation from phenol-degrading bacteria as a promising strategy for efficient phenol removal from soil while promoting plant growth and health.IMPORTANCEThis study is significant for environmental remediation and agriculture by its exploration of a more environmentally friendly and cost-effective bio-strategy in treating phenol-contaminated soil. These findings have essential implications for environmental remediation efforts and sustainable agriculture. By utilizing the biodegradation capabilities of Myroides xuanwuensis strain H13, it is possible to remove phenol contaminants from the soil efficiently, reducing their negative effects. Furthermore, the enhanced growth and health of the Chinese cabbage plants indicate the potential of this approach to promote sustainable crop production.

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

In this paper, we investigated the problem of describing the form of higher Jordan triple derivations on trivial extension algebras. We show that every higher Jordan triple derivation on a $ 2 $-torsion free $ * $-type trivial extension algebra is a sum of a higher derivation and a higher anti-derivation. As for its applications, higher Jordan triple derivations on triangular algebras are characterized.

Sitobion avenae F. is a highly prevalent and devastating pest in wheat crops, leading to significant yield losses. Silicon (Si) has been widely recognized as an effective inducer of plant resistance against aphids. Nevertheless, the underlying mechanisms governing the physiological and biochemical responses of plants induced by Si defense against S. avenae F. remain incompletely understood. In this study, we conducted experiments by treating wheat leaves with varying concentrations of Tetraethyl orthosilicate (TEOS) spray under aphid infestation. We meticulously observed and recorded the life cycle of S. avenae F. and measured the content of plant hormones, secondary metabolites, and the activity of defense enzymes in wheat leaves. Furthermore, we utilized structural equation modeling to discern the causal correlation between aphid performance and the physiological-biochemical responses of wheat under TEOS sprays. Our findings revealed that a concentration of 3 mmol/L TEOS significantly shortened the net reproductive rate, intrinsic rate and finite rate of increase, and mean generation time of S. avenae F., while simultaneously prolonging the population doubling time. Additionally, the content of lignin, total phenolics, flavonoids, alkaloids, tannin, jasmonic acid (JA), and salicylic acid in wheat leaves exhibited a substantial increase. Furthermore, the activity of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), catalase, and lipoxygenase in wheat leaves was significantly enhanced. Our results suggest that TEOS spray reduced the survival and population growth of S. avenae F. while enhancing the defense response of wheat against aphids by activating the activity of PAL and PPO in wheat, and increasing the content of total phenolic and JA. This work provides valuable insights for the development of appropriate Si fertilizers for effective pest management and offers robust theoretical support for wheat aphid control through agricultural fertilization strategies.

Polygala tenuifolia, commonly known as Yuanzhi (YZ) in Chinese, has been shown to possess anti-insomnia properties. However, the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear. Herein, we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging (MSI)-based spatial resolved metabolomics. According to the results, 17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain, which might be the major components contributing to the sedative-hypnotic effects. Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse, and dopaminergic synapse, among other pathways. LC-MS/MS-based targeted metabolomics and Western blot (WB) revealed that tryptophan-serotonin-melatonin (Trp-5-HT-Mel) and tyrosine-norepinephrine-adrenaline (Tyr-Ne-Ad) are the key regulated pathways. Dopa decarboxylase (DDC) upregulation and phenylethanolamine N-methyltransferase (PNMT) downregulation further confirmed these pathways. Furthermore, MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland (PG), and Ad in the brainstem, including the middle brain (MB), pons (PN), and hypothalamus (HY). In summary, this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine, YZ.

ABSTRACT Skin ulceration syndrome (SUS) is currently the main disease threatening Apostichopus japonicus aquaculture due to its higher mortality rate and infectivity, which is caused by Vibrio splendidus. Our previous studies have demonstrated that SUS is accompanied by intestinal microbiota (IM) dysbiosis, alteration of short-chain fatty acids (SCFAs) content and the damage to the intestinal barrier. However, the mediating effect of IM on intestine dysfunction is largely unknown. Herein, we conducted comprehensive intestinal microbiota transplantation (IMT) to explore the link between IM and SUS development. Furthermore, we isolated and identified a Bacillus coagulans strain with an ability to produce acetic acid from both healthy individual and SUS individual with IM from healthy donors. We found that dysbiotic IM and intestinal barrier function in SUS recipients A. japonicus could be restored by IM from healthy donors. The B. coagulans strain could restore IM community and intestinal barrier function. Consistently, acetate supply also restores intestinal homeostasis of SUS-diseased and V. splendidus-infected A. japonicus. Mechanically, acetate was found to specifically bind to its receptor-free fatty acid receptor 2 (FFAR2) to mediate IM structure community and intestinal barrier function. Knockdown of FFAR2 by transfection of specific FFAR2 siRNA could hamper acetate-mediated intestinal homeostasis in vivo. Furthermore, we confirmed that acetate/FFAR2 could inhibit V. splendidus-activated NF-κB–MLCK–MLC signaling pathway to restore intestinal epithelium integrity and upregulated the expression of ZO-1 and Occludin. Our findings provide the first evidence that B. coagulans restores pathogen-induced intestinal barrier dysfunction via acetate/FFAR2–NF-κB–MLCK–MLC axis, which provides new insights into the control and prevention of SUS outbreak from an ecological perspective.IMPORTANCESkin ulceration syndrome (SUS) as a main disease in Apostichopus japonicus aquaculture has severely restricted the developmental A. japonicus aquaculture industry. Intestinal microbiota (IM) has been studied extensively due to its immunomodulatory properties. Short-chain fatty acids (SCFAs) as an essential signal molecule for microbial regulation of host health also have attracted wide attention. Therefore, it is beneficial to explore the link between IM and SUS for prevention and control of SUS. In the study, the contribution of IM to SUS development has been examined. Additionally, our research further validated the restoration of SCFAs on intestinal barrier dysfunction caused by SUS via isolating SCFAs-producing bacteria. Notably, this restoration might be achieved by inhibition of NF-κB–MLCK–MLC signal pathway, which could be activated by V. splendidus. These findings may have important implications for exploration of the role of IM in SUS occurrence and provide insight into the SUS treatment.

Evaluating toxicity and decoding the underlying mechanisms of active compounds are crucial for drug development. In this study, we present an innovative, integrated approach that combines air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and spatial metabolomics to comprehensively investigate the nephrotoxicity and underlying mechanisms of nitidine chloride (NC), a promising anti-tumor drug candidate. Our quantitive AFADESI-MSI analysis unveiled the region specific of accumulation of NC in the kidney, particularly within the inner cortex (IC) region, following single and repeated dose of NC. High spatial resolution ToF-SIMS analysis further allowed us to precisely map the localization of NC within the renal tubule. Employing spatial metabolomics based on AFADESI-MSI, we identified over 70 discriminating endogenous metabolites associated with chronic NC exposure. These findings suggest the renal tubule as the primary target of NC toxicity and implicate renal transporters (organic cation transporters, multidrug and toxin extrusion, and organic cation transporter 2 (OCT2)), metabolic enzymes (protein arginine N-methyltransferase (PRMT) and nitric oxide synthase), mitochondria, oxidative stress, and inflammation in NC-induced nephrotoxicity. This study offers novel insights into NC-induced renal damage, representing a crucial step towards devising strategies to mitigate renal damage caused by this compound.

Low temperature is a common abiotic stress that causes significant damage to crop production. Polyamines (PAs) are a class of aliphatic amine compounds that serve as regulatory molecules involved in plant growth, development, and response to abiotic and biotic stresses. In this study, we found that the exogenous application of two concentrations of spermidine (Spd) significantly enhanced the freezing tolerance of three differently matured rapeseed (Brassica napus L.) varieties, as manifested by higher survival rates, lower freezing injury indexes, and reduced H2O2 content. RNA-seq and qRT-PCR analyses showed that Spd enhanced the freezing tolerance of rapeseed by regulating genes related to the PA metabolic pathway and antioxidant mechanism, and generally inhibited the expression of genes related to the JA signaling pathway. This study provides a reference basis for understanding the functionality and molecular mechanisms of polyamines in the response of rapeseed to freezing stress.

Cogeneration is an important means for heat supply enterprises to obtain heat, and accurate load prediction is particularly crucial. The heat load of a centralized heat supply system is influenced by various factors such as outdoor meteorological parameters, the building envelope structure, and regulation control, which exhibit a strong coupling and nonlinearity. It is essential to identify the key variables affecting the heat load at different heating stages through data mining techniques and to use deep learning algorithms to precisely regulate the heating system based on load predictions. In this study, a heat station in a northern Chinese city is taken as the subject of research. We apply the Fuzzy Clustering based on Fourier distance (FCBD-FCM) algorithm to transform the factors influencing the long and short-term load prediction of heat supply from the time domain to the frequency domain. This transformation is used to analyze the degree of their impact on load changes and to extract factors with significant influence as the multifeatured input variables for the prediction model. Five neural network models for load prediction are established, namely, Backpropagation (BP), convolutional neural network (CNN), Long Short-Term Memory (LSTM), CNN-LSTM, and CNN-BiLSTM. These models are compared and analyzed for their performance in long-term, short-term, and ultrashort-term heating load prediction. The findings indicate that the load prediction accuracy is high when multifeatured input variables are based on fuzzy clustering. Furthermore, the CNN-BiLSTM model notably enhances the prediction accuracy and generalization ability compared to other models, with the Mean Absolute Percentage Error (MAPE) averaging within 3%.

Background: Lipopolysaccharide (LPS) is related to various cardiovascular diseases. However, the relationship between LPS and new-onset atrial fibrillation (NOAF) after ST-segment elevation myocardial infarction (STEMI) has yet to be elucidated. This study aimed to evaluate the impact of LPS on NOAF in STEMI patients. Methods: This was a single-center retrospective observational study including 806 patients diagnosed with STEMI. LPS levels were determined using a commercial ELISA kit. NOAF was characterized by postadmission AF with the absence of any prior history of AF. Results: A total of 806 participants were enrolled, with 752 individuals in the non-AF group (93.3%) and 54 individuals in the AF group (6.7%). Multivariable analysis showed that LPS (OR = 1.047; 95% CI: 1.029–1.065, P

To enhance the understanding of yield-related traits in tetraploid wheat, it is crucial to investigate and identify genes that govern superior yield characteristics. This study utilized the wheat55K single nucleotide polymorphism array to genotype a recombinant inbred line (RIL) population consisting of 120 lines developed through the crossbreeding of two tetraploid wheat varieties, Qin Hei-1 (QH-1) and Durum Wheat (DW). An investigation and analysis were conducted on 11 yield-related traits, including peduncle length (PL), neck length (NL), spike length (SL), flowering date (FD), heading date (HD), thousand-kernel weight (TKW), kernel area ratio (KAR), kernel circumference (KC), kernel length (KL), kernel width (KW), and kernel length–width ratio (KL-WR), over a period of three years in two locations, Yang Ling, Shaanxi, and Lin He, Inner Mongolia. The analysis identified nine stable loci among eight agronomic traits, named QSL.QD-1A.1, QNL.QD-4B.2, QPL.QD-4B.1, QFD.QD-2B, QHD.QD-2B.1, QHD.QD-4B, QKC.QD-4B.2, QKL-WR.QD-4B.6, and QKL.QD-4B.2. Among them, the additive effects of three QTLs, QSL.QD-1A.1, QNL.QD-4B.2, and QFD.QD-2B, were positive, indicating that the enhancing alleles at these loci were derived from the parent line QH-1. These three QTLs showed significant positive effects on the phenotypes of the population materials. Furthermore, potential functional genes were identified within the mapping intervals of QSL.QD-1A.1 and QNL.QD-4B.2, which regulate the development of spike length and neck length, respectively. These results provide potential QTLs and candidate genes, which broaden the genetic basis of agronomic traits related to yield, such as SL, NL, PL, and FD, and benefits for wheat breeding and improvement.

When heating units are operated in winter, the extreme conditions, such as deep peak regulation and large extraction, can easily lead to a low unit load and severe icing in the wet cooling tower, which threatens the safe operation of the unit. Therefore, it is necessary to study the anti-freezing characteristics of the wet cooling tower. In this paper, a three-dimensional numerical model of a high-level, natural draft wet cooling tower is developed based on the constant heat load method. The influence of withdrawing a certain percentage of circulating water into the bypass on the cooling performance and anti-freezing characteristics of the high-level, natural draft wet cooling tower is investigated. The results show that as the percentage of circulating water bypass extraction increases, the temperature drop of circulating water in the tower continues to increase, but the lowest and the average water temperatures at the bottom of the packing continue to decrease. At the same time, the amount of circulating water entering the tower decreases, the pressure difference between the inside and outside of the tower under the same environmental conditions decreases, and the pumping force of the cooling tower decreases. If the circulating water bypass extraction percentage is less than 10%, it can prevent the circulating water from freezing at the bottom of the packing and, at the same time, try to reduce the temperature of the circulating water entering the condenser to ensure the efficiency of the unit.

To investigate the effects of individual essential amino acids (EAA) on growth and the underlying mechanisms, EAA individually supplemented a low-protein (LP) diet fed to young rats in the present study. Treatments were an LP diet that contained 6% crude protein (CP), a high-protein (HP) diet that contained 18% CP, and 10 LP diets supplemented with individual EAA to achieve an EAA supply equal to that of the HP diet. The CP concentration of the LP diet was ascertained from the results of the first experiment, which examined the effects of dietary CP concentrations on growth rates, with CP ranging from 2% to 26%. Weight gain was increased with the supplementation of His, Ile, Lys, Thr, or Trp as compared to the LP diet (p < 0.05). Feed intake was greater for the His-, Lys-, and Thr-supplemented treatments as compared to the LP group (p < 0.05). Protein utilization efficiency was lower for the HP group than other groups (p < 0.01). The supplementation of Leu, Lys, and Val led to reduced protein utilization efficiency (p < 0.05), but the supplementation of Thr and Trp led to greater efficiency than the LP group (p < 0.05). Compared to the LP group, plasma urea concentrations were elevated with individual EAA supplementation, with the exception of the Thr addition. The added EAA resulted in increased concentrations of the corresponding EAA in plasma, except for Arg and Phe supplementation. The supplementation of Arg, His, Leu, Lys, and Met individually stimulated mTORC1 pathway activity (p < 0.05), and all EAA resulted in the decreased expression of ATF4 (p < 0.05). In summary, the supplementation of His, Ile, Lys, Thr, or Trp to an LP diet improved the growth performance of young rats. Responses to His and Lys additions were related to the activated mTORC1 pathway and feed intake increases. The improved growth performance resulting from the addition of a single EAA is not solely attributed to the increased plasma availability of EAA. Rather, it may be the consequence of a confluence of factors encompassing signaling pathways, the availability of amino acids, and other associated elements. The additivity of these factors results in independent responses to several EAA with no order of limitation, as is universally encoded in growth models for all production animal species.

SMXL genes constitute a conserved gene family that is ubiquitous in angiosperms and involved in regulating various plant processes, including branching, leaf elongation, and anthocyanin biosynthesis, but little is known about their molecular functions in pear branching. Here, we performed genome-wide identification and investigation of the SMXL genes in 16 angiosperms and analyzed their phylogenetics, structural features, conserved motifs, and expression patterns. In total, 121 SMXLs genes were identified and were classified into four groups. The number of non-redundant SMXL genes in each species varied from 3 (Amborella trichopoda Baill.) to 18 (Glycine max Merr.) and revealed clear gene expansion events over evolutionary history. All the SMXL genes showed conserved structures, containing no more than two introns. Three-dimensional protein structure prediction revealed distinct structures between but similar structures within groups. A quantitative real-time PCR analysis revealed different expressions of 10 SMXL genes from pear branching induced by fruit-thinning treatment. Overall, our study provides a comprehensive investigation of SMXL genes in the Rosaceae family, especially pear. The results offer a reference for understanding the evolutionary history of SMXL genes and provide excellent candidates for studying fruit tree branching regulation, and in facilitating pear pruning and planting strategies.

Thermal power units play a crucial role in the deep peak regulation of power generation. During deep peak regulation, the load of the unit changes significantly, causing fluctuations in the inlet water temperature of the cooling tower and the water temperature in the filler. Therefore, in cold regions in winter, cooling towers have a high risk of freezing, which threatens the economic and safe operation of the unit. This paper establishes a three-dimensional numerical model based on constant heat dissipation and explores the average and minimum water temperatures at the bottom of filler under different water distribution methods, crosswind velocities, and ambient temperatures. The results show that the water distribution method has a significant impact on the water temperature at the filler bottom. Reducing the water distribution area can significantly increase the minimum water temperature at the filler bottom and reduce the risk of freezing. Although the presence of crosswind is not conducive to the cooling performance of the cooling tower, the higher the crosswind velocity, the higher the minimum outlet water temperature at the filler bottom and the lower the risk of freezing. The minimum water temperature at the filler bottom is approximately linearly related to the ambient temperature and is less affected by the unit load at the same temperature.