Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity.

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Adaptation in Unstable Environments and Global Gene Losses: Small but Stable Gene Networks by the May-Wigner Theory.

Although gene loss is common in evolution, it remains unclear whether it is an adaptive process. In a survey of seven major mangrove clades that are woody plants in the intertidal zones of daily environmental perturbations, we noticed that they generally evolved reduced gene numbers. We then focused on the largest clade of Rhizophoreae and observed the continual gene set reduction in each of the eight species. A great majority of gene losses are concentrated on environmental interaction processes, presumably to cope with the constant fluctuations in the tidal environments. Genes of the general processes for woody plants are largely retained. In particular, fewer gene losses are found in physiological traits such as viviparous seeds, high salinity, and high tannin content. Given the broad and continual genome reductions, we propose the May-Wigner theory (MWT) of system stability as a possible mechanism. In MWT, the most effective solution for buffering continual perturbations is to reduce the size of the system (or to weaken the total genic interactions). Mangroves are unique as immovable inhabitants of the compound environments in the land-sea interface, where environmental gradients (such as salinity) fluctuate constantly, often drastically. Extending MWT to gene regulatory network (GRN), computer simulations and transcriptome analyses support the stabilizing effects of smaller gene sets in mangroves vis-à-vis inland plants. In summary, we show the adaptive significance of gene losses in mangrove plants, including the specific role of promoting phenotype innovation and a general role in stabilizing GRN in unstable environments as predicted by MWT.

One-Dimensional Crystal-Structure Te-Se Alloy for Flexible Shortwave Infrared Photodetector and Imaging.

Flexible shortwave infrared detectors play a crucial role in wearable devices, bioimaging, automatic control, etc. Commercial shortwave infrared detectors face challenges in achieving flexibility due to the high fabrication temperature and rigid material properties. Herein, we develop a high-performance flexible Te0.7Se0.3 photodetector, resulting from the unique 1D crystal structure and small elastic modulus of Te-Se alloying. The flexible photodetector exhibits a broad-spectrum response ranging from 365 to 1650 nm, a fast response time of 6 µs, a broad linear dynamic range of 76 dB, and a specific detectivity of 4.8 × 1010 Jones at room temperature. The responsivity of the flexible detector remains at 93% of its initial value after bending with a small curvature of 3 mm. Based on the optimized flexible detector, we demonstrate its application in shortwave infrared imaging. These results showcase the great potential of Te0.7Se0.3 photodetectors for flexible electronics.

Genome-wide analysis of the SWEET gene family in Hemerocallis citrina and functional characterization of HcSWEET4a in response to salt stress.

Sugars will be eventually effluxed transporters (SWEETs) have been confirmed to play diverse physiological roles in plant growth, development and stress response. However, the characteristics and functions of the SWEET genes in Hemerocallis citrina remain unclear and poorly elucidated. In this study, the whole genome of Hemerocallis citrina was utilized to conduct bioinformatics analysis and a total of 19 HcSWEET genes were successfully identified. Analysis of the physicochemical properties indicated dominant differences among these HcSWEETs. A phylogenetic analysis revealed that HcSWEET proteins can be divided into 4 clades ranging from Clade I to IV, where proteins within the same clade exhibited shared conserved motifs and gene structures. Five to six exons were contained in the majority of HcSWEET genes, which were unevenly distributed across 11 chromosomes. The gene duplication analysis showed the presence of 4 gene pairs. Comparative syntenic maps revealed that the HcSWEET gene family might present more closed homology in monocotyledons than dicotyledons. Cis-acting element analysis of HcSWEET genes indicated key responsiveness to various hormones, light, and stresses. Additionally, transcriptome sequencing analysis suggested that most HcSWEET genes had a relatively higher expression in roots, and HcSWEET4a was significantly up-regulated under salt stress. Overexpression further verified the possibility that HcSWEET4a was involved in response to salt stress, which provides novel insights and facilitates in-depth studies of the functional analysis of HcSWEETs in resistance to abiotic stress.

The pan-plastome of Hemerocallis citrina reveals new insights into the genetic diversity and cultivation history of an economically important food plant.

BACKGROUND: Hemerocallis citrina Baroni (Huang hua cai in Chinese) is a perennial herbaceous plant grown for its flower buds that are eaten fresh or dried and is known as the vegetarian three treasures. The nuclear genome of H. citrina has been reported, but the intraspecific variation of the plastome (plastid genome) has not yet been studied. Therefore, the panplastome of this species collected from diverse locations is reported here for the first time. RESULTS: In this study, 65 H. citrina samples were resequenced, de novo assembled, and aligned with the published plastome of H. citrina to resolve the H. citrina panplastome. The sizes of the 65 newly assembled complete plastomes of H. citrina ranged from 156,048 bp to 156,263 bp, and the total GC content ranged from 37.31 to 37.34%. The structure of the complete plastomes showed a typical tetrameric structure, including a large single copy (LSC), a small single copy (SSC), and a pair of inverted repeat regions (IRA and IRB). Many nucleotide variants were identified between plastomes, among which the variants in the intergenic spacer region were the most abundant, with the highest number of variants concentrated in the LSC region. Based on the phylogenetic tree constructed using the ML method, population structure analysis, and principal component analysis (PCA), the panplastome data were subdivided into five genetic clusters. The C5 genetic cluster was mostly represented by samples from Qidong, Hunan Province, while samples from Shanxi and Shaanxi Provinces were classified into the C4 genetic cluster. The greatest genetic diversity was found in the C1 genetic cluster, and the greatest genetic distance between any two clusters was found between the C4 and C5 clusters. CONCLUSION: The resolution of the panplastome and the analysis of the population structure of H. citrina plastomes provide important data for future breeding projects and germplasm preservation.

Growth of BiSBr Microsheet Arrays for Enhanced Photovoltaics Performance.

In this study, single-crystalline BiSBr is synthesized using a solution-based approach and conducted a systematic characterization of its photoelectric properties and photovoltaic performances. UV photoelectron spectroscopy and density functional theory (DFT) calculations reveal that BiSBr is an indirect p-type semiconductor, characterized by distinct positions and compositions of the valence band maximum and conduction band minimum. The BiSBr single crystal microrod features a significant electrical conductivity of 14 800 S m-1 along the c-axis, denoting minimal carrier resistance in this direction. For photovoltaic performance assessment, the authors successfully fabricated two homogeneous BiSBr films on TiO2 porous substrates: A microsheet array film via physical vapor deposition (PVD) and solvothermal treatment, and a BiSBr microsheet film via PVD and thermal treatment. The solar cell, comprising a BiSBr microsheet array film with an architecture of fluorine-doped tin oxide FTO/TiO2/BiSBr/(I3 -/I-)/Pt, demonstrated a power conversation efficiency of 1.40%, ≈11 times that of BiSBr microsheet film counterpart. These preliminary results underscore the potential of BiSBr microsheet arrays, producible through low-cost solution processes, as adept light absorbers, enhancing photovoltaic efficiency through effective light scattering and promoting efficient electron-hole separation and transport.

Intrinsic microbial temperature sensitivity and soil organic carbon decomposition in response to climate change.

Soil microbes are essential for regulating carbon stocks under climate change. However, the uncertainty surrounding how microbial temperature responses control carbon losses under warming conditions highlights a significant gap in our climate change models. To address this issue, we conducted a fine-scale analysis of soil organic carbon composition under different temperature gradients and characterized the corresponding microbial growth and physiology across various paddy soils spanning 4000 km in China. Our results showed that warming altered the composition of organic matter, resulting in a reduction in carbohydrates of approximately 0.026% to 0.030% from humid subtropical regions to humid continental regions. These changes were attributed to a decrease in the proportion of cold-preferring bacteria, leading to significant soil carbon losses. Our findings suggest that intrinsic microbial temperature sensitivity plays a crucial role in determining the rate of soil organic carbon decomposition, providing insights into the temperature limitations faced by microbial activities and their impact on soil carbon-climate feedback.

IVF laboratory management through workflow-based RFID tag witnessing and real-time information entry.

BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.

Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China.

Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.

Cooperative Rh/Achiral Phosphoric Acid-Enabled [3+3] Cycloannulation of Carbonyl Ylides with Quinone Monoimines: Synthesis of Benzofused Dioxabicyclo[3.2.1]octane Scaffolds.

A cooperative Rh/achiral phosphoric acid-enabled [3+3] cycloaddition of in situ-generated carbonyl ylides with quinone monoimines has been developed. With the ability to build up the molecular complexity rapidly and efficiently, this method furnishes highly functionalized oxa-bridged benzofused dioxabicyclo[3.2.1]octane scaffolds bearing two quaternary centers in good to excellent yields under mild conditions. Moreover, the utility of the current method was demonstrated by gram-scale synthesis and elaboration of the products into various functionalized oxa-bridged heterocycles.

The gap between statistical and clinical significance: time to pay attention to clinical relevance in patient-reported outcome measures of insomnia.

BACKGROUND: Appropriately defining and using the minimal important change (MIC) and the minimal clinically important difference (MCID) are crucial for determining whether the results are clinically significant. The aim of this study is to survey the status of randomized controlled trials (RCTs) for insomnia interventions to assess the inclusion and interpretation of MIC/MCID values. METHODS: We conducted a cross-sectional study to survey the status of RCTs for insomnia interventions to assess the inclusion and appropriate interpretation of MIC/MCID values. A literature search was conducted by searching the main sleep medicine journals indexed in PubMed, the Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify a broad range of search terms. We included RCTs with no restriction on the intervention. The included studies used the Insomnia Severity Index (ISI) or the Pittsburgh Sleep Quality Index (PSQI) questionnaire as the outcome measures. RESULTS: 81 eligible studies were identified, and more than one-third of the included studies used MIC/MCID (n = 31, 38.3%). Among them, 21 studies with ISI as the outcome used MIC defined as a relative decrease ranging from 3 to 8 points. The most frequently used MIC value was a 6-point decrease (n = 7), followed by 8-point (n = 6) and 7-point decrease (n = 4), a 4 to 5-points decrease (n = 3), and a 30% reduction from baseline; 6 studies used MCID values, ranging from 2.8 to 4 points. The most frequently used MCID value was a 4-point decrease in the ISI (n = 4). 4 studies with PSQI as the outcome used a 3-point change as the MIC (n = 2) and a 2.5 to 2.7-point difference as MCID (n = 2). 4 non-inferiority design studies considered interval estimation when drawing clinically significant conclusions in their MCID usage. CONCLUSIONS: The lack of consistent MIC/MCID interpretation and usage in outcome measures for insomnia highlights the urgent need for further efforts to address this issue and improve reporting practices.

Restoration of HMGCS2-mediated ketogenesis alleviates tacrolimus-induced hepatic lipid metabolism disorder.

Tacrolimus, one of the macrolide calcineurin inhibitors, is the most frequently used immunosuppressant after transplantation. Long-term administration of tacrolimus leads to dyslipidemia and affects liver lipid metabolism. In this study, we investigated the mode of action and underlying mechanisms of this adverse reaction. Mice were administered tacrolimus (2.5 mg·kg-1·d-1, i.g.) for 10 weeks, then euthanized; the blood samples and liver tissues were collected for analyses. We showed that tacrolimus administration induced significant dyslipidemia and lipid deposition in mouse liver. Dyslipidemia was also observed in heart or kidney transplantation patients treated with tacrolimus. We demonstrated that tacrolimus did not directly induce de novo synthesis of fatty acids, but markedly decreased fatty acid oxidation (FAO) in AML12 cells. Furthermore, we showed that tacrolimus dramatically decreased the expression of HMGCS2, the rate-limiting enzyme of ketogenesis, with decreased ketogenesis in AML12 cells, which was responsible for lipid deposition in normal hepatocytes. Moreover, we revealed that tacrolimus inhibited forkhead box protein O1 (FoxO1) nuclear translocation by promoting FKBP51-FoxO1 complex formation, thus reducing FoxO1 binding to the HMGCS2 promoter and its transcription ability in AML12 cells. The loss of HMGCS2 induced by tacrolimus caused decreased ketogenesis and increased acetyl-CoA accumulation, which promoted mitochondrial protein acetylation, thereby resulting in FAO function inhibition. Liver-specific HMGCS2 overexpression via tail intravenous injection of AAV8-TBG-HMGCS2 construct reversed tacrolimus-induced mitochondrial protein acetylation and FAO inhibition, thus removing the lipid deposition in hepatocytes. Collectively, this study demonstrates a novel mechanism of liver lipid deposition and hyperlipidemia induced by long-term administration of tacrolimus, resulted from the loss of HMGCS2-mediated ketogenesis and subsequent FAO inhibition, providing an alternative target for reversing tacrolimus-induced adverse reaction.

Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.

Identification of polymorphic markers for germplasm conservation of three precious Chinese palace goldfish using whole-genome sequencing.

China was the first country in the world to breed goldfish and has generated many unique goldfish varieties, including the most aristocratic Chinese palace goldfish. Due to the lack of scientific research on Chinese palace goldfish, their selection and breeding are mainly carried out through traditional hybridization, leading to serious inbreeding and the degradation of germplasm resources. To this end, whole-genome resequencing was performed to understand the genetic variation among three different varieties (eggpompons, goosehead, and tigerhead) from nine core conserved populations in China. A total of 15 polymorphic SSRs were developed for population genetics, and all tested populations were considered moderately polymorphic with an average polymorphism information content value of 0.4943. Genetic diversity in different varieties showed that all conserved populations were well protected with the potential for continued exploitation. This study provides reliable molecular tools and a basis for designing conservation and management programs in Chinese palace goldfish.

Finite element analysis of precise puncture vertebral augmentation in the treatment of different types of osteoporotic vertebral compression fractures.

BACKGROUND: Osteoporosis vertebral compression fracture (OVCF) secondary to osteoporosis is a common health problem in the elderly population. Vertebral augmentation (VA) has been widely used as a minimally invasive surgical method. The transpedicle approach is commonly used for VA puncture, but sometimes, it is limited by the anatomy of the vertebral body and can not achieve good surgical results. Therefore, we propose the treatment of OVCF with precise puncture vertebral augmentation (PPVA). This study used finite element analysis to explore the biomechanical properties of PPVA in the treatment of osteoporotic vertebral compression fractures (OVCFs) with wedge, biconcave, and collapse deformities. METHOD: Three-dimensional finite element models of the fractured vertebral body and adjacent superior and inferior vertebral bodies were established using Computed Tomography (CT) data from patients with OVCF, both before and after surgery. Evaluate the stress changes of the wedged deformed vertebral body, biconcave deformed vertebral body, collapsed deformed vertebral body, and adjacent vertebral bodies before and after PPVA. RESULT: In vertebral bodies with wedge deformity and collapsed deformity, PPVA can effectively reduce the stress on the vertebral body but increases the stress on the vertebral body with biconcave deformity. PPVA significantly decreases the stress on the adjacent vertebral bodies of the wedge deformed vertebral body, and decreases the stress on the adjacent superior vertebral body of biconcave deformity and collapsed deformed vertebral bodies, but increases the stress on the adjacent inferior vertebral bodies. PPVA improves the stress distribution of the vertebral body and prevents high-stress areas from being concentrated on one side of the vertebral body. CONCLUSION: PPVA has shown positive surgical outcomes in treating wedge deformed and collapsed deformed vertebral bodies. However, its effectiveness in treating biconcave vertebral body is limited. Furthermore, PPVA has demonstrated favorable results in addressing adjacent superior vertebral body in three types of fractures.

Biomechanical study between percutaneous vertebroplasty combined with cement pedicle plasty improves vertebral biomechanical stability: A finite element analysis.

OBJECTIVE: To investigate the biomechanical effects of percutaneous vertebroplasty combined with cement pedicle plasty (PVCPP) on the unstable osteoporotic vertebral fractures (OVFs) through finite element (FE) analysis. The study compares the biomechanical stability of finite element models between percutaneous vertebroplasty (PVP) and percutaneous vertebroplasty combined with cement pedicle plasty. METHODS: Two patients with unstable OVFs underwent computed tomography (CT) examination at the thoracolumbar vertebral body levels, respectively. The CT images were reconstructed into three-dimensional finite element models to simulate stress conditions across six dimensions and to evaluate the vertebral von Mises stress before and after bone cement reinforcement. RESULTS: The study found that stress distribution differed between groups mainly at the pedicle base. In the surgical vertebral bodies, the maximum stress in the PVP group decreased during flexion and left bending, while it increased in other states. In the PVCPP group, all maximum stresses decreased. In the inferior vertebral bodies, the maximum stress in the PVP group generally increased, while it decreased in the PVCPP group. In the superior vertebral bodies, postoperatively, the maximum stress in the PVP group generally increased, while it almost remained unchanged in the PVCPP group. PVP group had higher cement stress and displacement. CONCLUSION: PVCPP is an effective treatment method for patients with unstable OVFs. It can quickly relieve pain and enhance the stability of the three columns, thereby reducing the risk of some complications.

Machine learning-based analysis of heavy metal contamination in Chinese lake basin sediments: Assessing influencing factors and policy implications.

Sediments are important heavy metal sinks in lakes, crucial for ensuring water environment safety. Existing studies mainly focused on well-studied lakes, leaving gaps in understanding pollution patterns in specific basins and influencing factors.We compiled comprehensive sediment contamination data from literature and public datasets, including hydro-geomorphological, climatic, soil, landscape, and anthropogenic factors. Using advanced machine learning, we analyzed typical pollution factors to infer potential sources and migration pathways of pollutants and predicted pollution levels in basins with limited data availability. Our analysis of pollutant distribution data revealed that Cd had the most extensive pollution range, with the most severe pollution occurring in the Huaihe and Yangtze River basins. Furthermore, we identified distinct groups of driving factors influencing various heavy metals. Cd, Cr, and Pb were primarily influenced by human activities, while Cu and Ni were affected by both anthropogenic and natural factors, and Zn tended more towards natural sources. Our predictions indicated that, in addition to the typical highly polluted areas, the potential risk of Cd, Cu and Ni is higher in Xinjiang, and in Tibet and Qinghai, the potential risk of Cd, Cr, Cu and Ni is higher. Pb and Zn presented lower risks, except in the Huaihe and Yangtze River Basins. Temperature, wind, precipitation, precipitation rate, and the cation exchange capacity of soil significantly impacted the predictions of heavy metal pollution in sediments, suggesting that particulate migration, rainfall runoff, and soil erosion are likely the main pathways for pollutant migration into sediments. Considering the migration, pathways, and sources of pollutants, we propose strategies such as low-impact development and promoting sustainable transportation to mitigate pollution. This study provides the latest insights into heavy metal pollution in Chinese lake sediments, offering references for policy-making and water resource management.

Climate warming worsens thermal resource utilization for practical rice cultivation in China.

Rice production is sensitive to climate change and significantly affected by warming in recent years. To what extent climate warming shifted rice phenology and varied thermal resource condition were explored across five agro-ecological zones in China, based on up-to-date observations of meteorology and rice cultivation in 1981-2020. It was clearly signaled that there was a general advance of 0.3-3.8 days in observed sowing date and a delay of 0.4-3.5 days in observed maturity date in 2001-2020 relative to 1981-2000 in major zones. A vacant time slice of 2.6-28.8 days between observed sowing date and potential sowing date, and a lag of 15.4-56.7 days in potential maturity date compared to observed maturity date were identified in 2001-2020. Within longer growing season, useful accumulated temperature increased by 76.7-117.6 °C·d in 2001-2020 relative to 1981-2000, while disactive accumulated temperature also increased. In Northeast China, actual rice cultivation was undergoing earlier sowing date than potential sowing date and longer growing duration than potential duration, yet leading to upward disactive accumulated temperature. The decrease in the thermal resource utilization in 2001-2020 relative to 1981-2000 was highlighted at 55.3-78.3% stations in major zones, with a decrement of 0.006-0.018 in average magnitude. The changes in thermal resource utilization unveiled that the shifts in actual rice cultivation still could not compensate for the suitability in thermal resource utilization benefited from climate warming.

Salvianolic acid B alleviates autoimmunity in Treg-deficient mice via inhibiting IL2-STAT5 signaling.

Regulatory T cell (Treg) deficiency leads to immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, which is a CD4+ T cell-driven autoimmune disease in both humans and mice. Despite understanding the molecular and cellular characteristics of IPEX syndrome, new treatment options have remained elusive. Here, we hypothesized that salvianolic acid B (Sal B), one of the main active ingredients of Salvia miltiorrhiza, can protect against immune disorders induced by Treg deficiency. To examine whether Sal B can inhibit Treg deficiency-induced autoimmunity, Treg-deficient scurfy (SF) mice with a mutation in forkhead box protein 3 were treated with different doses of Sal B. Immune cells, inflammatory cell infiltration, and cytokines were evaluated by flow cytometry, hematoxylin and eosin staining and enzyme-linked immunosorbent assay Kits, respectively. Moreover, RNA sequencing, western blot, and real-time PCR were adopted to investigate the molecular mechanisms of action of Sal B. Sal B prolonged lifespan and reduced inflammation in the liver and lung of SF mice. Moreover, Sal B decreased plasma levels of several inflammatory cytokines, such as IL-2, IFN-γ, IL-4, TNF-α, and IL-6, in SF mice. By analyzing the transcriptomics of livers, we determined the signaling pathways, especially the IL-2-signal transducer and activator of transcription 5 (STAT5) signaling pathway, which were associated with Treg deficiency-induced autoimmunity. Remarkably, Sal B reversed the expression of gene signatures related to the IL-2-STAT5 signaling pathway in vitro and in vivo. Sal B prolongs survival and inhibits lethal inflammation in SF mice through the IL-2-STAT5 axis. Our findings may inspire novel drug discovery efforts aimed at treating IPEX syndrome.

Phytochemistry of Genus Buxus and Pharmacology of Cyclovirobuxine D.

BACKGROUND: Genus Buxus plants, commonly known as "boxwood", are widely distributed in China. The stems, branches, and leaves of the plant are traditionally used for rheumatism, toothache, chest pain, abdominal gas, and other diseases. However, an overview of the genus Buxus remains to be provided. PURPOSE: To provide a scientific basis for the appropriate use and further research the recent advancements in the traditional usage, phytochemistry, and, pharmacology of Buxus. STUDY DESIGN: Chemical composition and pharmacological correlation studies through a literature review. METHODS: Between 1970 and 2023, the available data concerning Buxus was compiled from online scientific sources, such as Sci-Finder, PubMed, CNKI, Google Scholar, and the Chinese Pharmacopoeia. Plant names were verified from "The Plant List" (http://www.theplantlist.org/). RESULTS: To date, 266 structurally diverse chemicals have been extracted and identified from the genus Buxus. Alkaloids constitute one of its primary bioactive phytochemicals. A summary of the channels of action of Cyclovirobuxine D on the cytotoxicity of a variety of cancers has been provided. CONCLUSION: Numerous findings from contemporary phytochemical and pharmacological studies support the traditional use, facilitating its application. Further research is necessary to address various shortcomings, including the identification of the active ingredients and quality control of the genus Buxus.