Transcription factor OsWRKY72 controls rice leaf angle by regulating LAZY1-mediated shoot gravitropism.

Leaf angle is a major trait of ideal architecture, which is considered to influence rice (Oryza sativa) cultivation and grain yield. Although a few mutants with altered rice leaf inclination angles have been reported, the underlying molecular mechanism remains unclear. In this study, we showed that a WRKY transcription factor gene, OsWRKY72, was highly expressed in the leaf sheath and lamina joint. Phenotypic analyses showed that oswrky72 mutants had smaller leaf angles than the wild type, while OsWRKY72 overexpression lines exhibited an increased leaf angle. This observation suggests that OsWRKY72 functions as a positive regulator, promoting the enlargement of the leaf angle. Our bioinformatics analysis identified LAZY1 as the downstream gene of OsWRKY72. Electrophoretic mobility shift assays and dual-luciferase analysis revealed that OsWRKY72 directly inhibited LAZY1 by binding to its promoter. Moreover, knocking out OsWRKY72 enhanced shoot gravitropism, which contrasted with the phenotype of lazy1 plants. These results imply that OsWRKY72 regulates the leaf angle through gravitropism by reducing the expression of LAZY1. In addition, OsWRKY72 could directly regulate the expression of other leaf angle-related genes such as FLOWERING LOCUS T-LIKE 12 (OsFTL12) and WALL-ASSOCIATED KINASE 11 (OsWAK11). Our study indicates that OsWRKY72 contributes positively to the expansion of the leaf angle by interfering with shoot gravitropism in rice.

Transcription factor OsWRKY11 induces rice heading at low concentrations but inhibits rice heading at high concentrations.

The heading date of rice is a crucial agronomic characteristic that influences its adaptability to different regions and its productivity potential. Despite the involvement of WRKY transcription factors in various biological processes related to development, the precise mechanisms through which these transcription factors regulate the heading date in rice have not been well elucidated. The present study identified OsWRKY11 as a WRKY transcription factor which exhibits a pivotal function in the regulation of the heading date in rice through a comprehensive screening of a clustered regularly interspaced palindromic repeats (CRISPR) ‒ CRISPR-associated nuclease 9 mutant library that specifically targets the WRKY genes in rice. The heading date of oswrky11 mutant plants and OsWRKY11-overexpressing plants was delayed compared with that of the wild-type plants under short-day and long-day conditions. Mechanistic investigation revealed that OsWRKY11 exerts dual effects on transcriptional promotion and suppression through direct and indirect DNA binding, respectively. Under normal conditions, OsWRKY11 facilitates flowering by directly inducing the expression of OsMADS14 and OsMADS15. The presence of elevated levels of OsWRKY11 protein promote formation of a ternary protein complex involving OsWRKY11, Heading date 1 (Hd1), and Days to heading date 8 (DTH8), and this complex then suppresses the expression of Ehd1, which leads to a delay in the heading date. Subsequent investigation revealed that a mild drought condition resulted in a modest increase in OsWRKY11 expression, promoting heading. Conversely, under severe drought conditions, a significant upregulation of OsWRKY11 led to the suppression of Ehd1 expression, ultimately causing a delay in heading date. Our findings uncover a previously unacknowledged mechanism through which the transcription factor OsWRKY11 exerts a dual impact on the heading date by directly and indirectly binding to the promoters of target genes.

Engineering the Metal/Oxide Interface of Pd Nanowire@CuOx Electrocatalysts for Efficient Alcohol Oxidation Reaction.

The development of new type electrocatalysts with promising activity and antipoisoning ability is of great importance for electrocatalysis on alcohol oxidation. In this work, Pd nanowire (PdNW)/CuOx heterogeneous catalysts with different types of PdOCu interfaces (Pd/amorphous or crystalline CuOx ) are prepared via a two-step hydrothermal strategy followed by an air plasma treatment. Their interface-dependent performance on methanol and ethanol oxidation reaction (MOR and EOR) is clearly observed. The as-prepared PdNW/crystalline CuOx catalyst with 17.2 at% of Cu on the PdNW surface exhibits better MOR and EOR activity and stability, compared with that of PdNW/amorphous CuOx and pristine PdNW catalysts. Significantly, both the cycling tests and the chronoamperometric measurements reveal that the PdNW/crystalline CuOx catalyst yields excellent tolerance toward the possible intermediates including formaldehyde, formic acid, potassium carbonate, and carbon monoxide generated during the MOR process. The detailed analysis of their chemical state reveals that the enhanced activity and antipoison ability of the PdNW/crystalline CuOx catalyst originates from the electron-deficient Pdδ+ active sites which gradually turn into Pd5 O4 species during the MOR catalysis. The Pd5 O4 species can likely be stabilized by moderate crystalline CuOx decorated on the surface of PdNW due to the strong PdOCu interaction.

Phytochemistry and pharmacological activities of Cannabis sativa fruit (Cannabis Fructus).

Cannabis sativa fruit (Cannabis Fructus) refers to the dried and ripe fruit of Cannabis sativa L. It is widely distributed in the northeast, North, and South China. It has medicinal, ecological, and economic values. This study aimed to review the chemical constituents and pharmacological activities of Cannabis Fructus, providing a reference for further exploration of Cannabis Fructus. Comprehensive information on Cannabis Fructus was collected via electronic searches (e.g., Google Scholar, PubMed, Sci Finder, and Web of Science) and from books on phytochemistry. Cannabis Fructus contains various compounds such as phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins, and polysaccharides. Its active ingredients exhibit anti-inflammatory, anti-oxidant, anti-bacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotective, lipoid-regulating, hepatoprotective, and immunomodulatory properties.

Study on the extraction, purification, stability, free radical scavenging kinetics, polymerization degree and characterization of proanthocyanidins from Pinus koraiensis seed scales.

To efficiently harness resources from Pinus koraiensis seed scales, a type of forestry waste, rigorous studies on the extraction, purification, stability, and free radical scavenging capacity of the proanthocyanidins derived from these seed scales were conducted. Kinetic models showed that under ultrasonic conditions, the proanthocyanidins content reached 2.66 mg/g within 0.5 h. The optimal storage parameters include darkness, 4 °C, and pH 4. The degrees of polymerization of the mixture and the high- and low-polymer components were 4.89, 7.42 and 3.07, respectively, with the low-polymer component exhibiting the highest radical scavenging activity. Through HPLC-QE-MS/MS, 1H NMR, and FT-IR analyses, we identified proanthocyanidin B1, proanthocyanidin B2, (-)-epicatechin, and polymeric trimer esters. The Pinus koraiensis proanthocyanidins exhibited a high molecular weight, a complex internal molecular structure, and commendable stability, with crystallization requiring elevated temperatures. Therefore, the proanthocyanidins from Pinus koraiensis seed scales have emerged as highly promising novel natural antioxidants.

Correlation between newborn weight and serum BCAAs in pregnant women with diabetes.

BACKGROUND: Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids for mammals. Maternal BCAAs during pregnancy have been associated with newborn development. Meanwhile, BCAAs have been tightly linked with insulin resistance and diabetes in recent years. Diabetes in pregnancy is a common metabolic disorder. The current study aims to assess the circulating BCAA levels in pregnant women with diabetes and their relationship with neonatal development. METHODS: The serum concentrations of BCAAs and their corresponding branched-chain α-keto acids (BCKAs) catabolites in 33 pregnant women with normal glucose tolerance, 16 pregnant women with type 2 diabetes before pregnancy (PDGM), and 15 pregnant women with gestational diabetes mellitus (GDM) were determined using a liquid chromatography system coupled to a mass spectrometer. The data were tested for normal distribution and homogeneity of variance before statistical analysis. Correlations were computed with the Pearson correlation coefficient. RESULTS: The maternal serum BCAAs and BCKAs levels during late pregnancy were higher in women with PGDM than those in healthy women. Meanwhile, the circulating BCAAs and BCKAs showed no significant changes in women with GDM compared with those in healthy pregnant women. Furthermore, the circulating BCAA and BCKA levels in women with PGDM were positively correlated with the weight of the newborn. The circulating leucine level in women with GDM was positively correlated with the weight of the newborn. BCAA and BCKA levels in healthy pregnant women showed no correlation with newborn weight. CONCLUSIONS: The serum BCAAs in pregnant women with diabetes, which was elevated in PGDM but not GDM, were positively correlated with newborn weight. These findings highlight potential approaches for early identification of high-risk individuals and interventions to reduce the risk of adverse pregnancy outcomes.

The correlation between HOMA-IR and cardiometabolic risk index among different metabolic adults: a cross-sectional study.

AIMS: This study aimed to explore the correlation between homeostasis model assessment of insulin resistance(HOMA-IR)and cardiometabolic risk index(CMRI) among different metabolic adults to evaluate the value of HOMA-IR in predicting cardiometabolic risk. METHODS: This cross-sectional study was conducted over 18 months (from August 1, 2020 to February 18, 2022) and included 1550 participants divided into non-metabolic syndrome (non-MetS) group (n = 628) and metabolic syndrome (MetS) group (n = 922) in three centers of China. Logistic regression analysis was employed to investigate the correlation between HOMA-IR, body fat percentage, BMI (body mass index), visceral fat index, waist-to-hip ratio, vitamin D, and CMRI. Further analysis was conducted to evaluate the ability of HOMA-IR in diagnosing high CMRI within different metabolic, gender, and age groups to predict the risk of cardiovascular disease (CVD). RESULTS: HOMA-IR was significantly higher in the MetS group compared with the non-MetS group (P < 0.05). CMRI was significantly higher in the MetS group compared to the non-MetS group (P < 0.05). According to ROC curve analysis, HOMA-IR can predict cardiovascular risk (CVR) in the general population, non-MetS individuals, and MetS people. Logistic regression analysis revealed that BMI, visceral fat index, waist-to-hip ratio, and HOMA-IR are independent risk indicators of high CVR, whereas vitamin D may exert a protective role. CONCLUSIONS: HOMA-IR was an independent risk factor for increased CVR in MetS patients. Moreover, HOMA-IR elevates the risk of CVD regardless of MetS and thus can be used for screening the general population. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry (Registration Number: ChiCTR2100054654).

Reflecting on the cardiac toxicity in non-small cell lung cancer in the era of immune checkpoint inhibitors therapy combined with thoracic radiotherapy.

In recent years, immune checkpoint inhibitors (ICIs) have become a widely used treatment for non-small cell lung cancer (NSCLC), and the combination with traditional radiotherapy (RT) has shown significant potential in prolonging patient survival. However, both thoracic RT and ICIs can lead to cardiac toxicity, including radiation-induced heart damage (RIHD) and immunotherapy-related heart damage (IRHD). It still remains uncertain whether the combination of thoracic RT and immunotherapy will exacerbate acute or late cardiovascular (CV) toxicity and incidence. In this review, we summarize safety data from relevant clinical studies regarding CV toxicity for the combination therapy in NSCLC patients, explore the underlying synergetic mechanisms and common risk factors, and proposed treatment and management strategies. We hope to increase emphasis on the long-term assessment of CV toxicity risks associated with the combination therapy, and reduce the incidence of CV deaths resulting from such regimens.

Arrhythmic events associated with immune checkpoint inhibitors therapy: A real-world study based on the Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Although arrhythmias have been reported in patients treated with immune checkpoint inhibitors (ICIs), the association between arrhythmias and ICIs has not been thoroughly evaluated in real-world studies. We aimed to describe the major features of ICI-related arrhythmic events and identify the factors that contributed to death. METHODS: A disproportionality analysis was performed using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 2011 to December 2021. Reporting odds ratios (RORs), proportional reporting ratio and information component were used to assess whether adverse arrhythmic events were associated with ICIs. The clinical characteristics of patients with ICI-associated arrhythmias were compared with fatal and non-fatal arrhythmias. The time to onset (TTO), fatality rates of arrhythmic events were also investigated. RESULTS: We identified a total of 1945 cases of ICI-related arrhythmic events. Men (64.78%) were identified significantly more frequently than women (28.84%). The median age was 68 years ([interquartile range, IQR] 60-75 years). Anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) were associated with adverse arrhythmic events, corresponding to ROR 1.11 (95% confidence interval [CI] 1.05-1.17) and ROR 1.34 (95% CI 1.20-1.49), respectively. However, anti-cytotoxic T-lymphocyte associated protein 4 or combination immunotherapy did not appear to be associated with arrhythmic events. Atrial fibrillation (N  = 576, 0.62%), cardiac arrest (N  = 284, 0.31%), tachycardia (N  = 175, 0.19%) were the most common adverse arrhythmic events. Sudden death and complete atrioventricular block are adverse events that are significantly associated with ICI-related arrhythmic events and have strong signal intensity. The TTO of cases that resulted in death (30 days [IQR] 11-73.75) was significantly earlier than that of cases that did not result in death (33 days [IQR 10.5-88.5], p  = 0.003). ICI-related arrhythmic events were severe with death occurring in 507 (26.07%) of 1945 arrhythmias cases. CONCLUSIONS: Treatment with PD-1/PD-L1 may cause arrhythmic events, which are severe and tend to occur early on during treatment. It is important to identify ICI-related arrhythmias as early as possible, and to manage them appropriately.

Microwave-accelerated cross-dehydrogenative-coupling (CDC) of N-(quinolin-8-yl)amides with acetone/acetonitrile under metal-free conditions.

A highly selective remote C(sp3)-H acetonation of N-(quinolin-8-yl)amide scaffolds at the C5-position under microwave irradiation has been developed. In the absence of a transition-metal-catalyst, benzoyl peroxide (BPO)-promoted cross-dehydrogenation coupling (CDC) of N-(quinolin-8-yl)amides with acetone/acetonitrile occurred smoothly to generate the corresponding 5-acetonated/acetonitriled N-(quinolin-8-yl)amides in good yields. The transformation is operationally simple, rapid, easily scaled-up to the gram scale, and shows a broad substrate scope.

Identification and characterization of Dof genes in Cerasus humilis.

Introduction: Dof genes encode plant-specific transcription factors, which regulate various biological processes such as growth, development, and secondary metabolite accumulation. Methods: We conducted whole-genome analysis of Chinese dwarf cherry (Cerasus humilis) to identify ChDof genes and characterize the structure, motif composition, cis-acting elements, chromosomal distribution, and collinearity of these genes as well as the physical and chemical properties, amino acid sequences, and phylogenetic evolution of the encoded proteins. Results: The results revealed the presence of 25 ChDof genes in C. humilis genome. All 25 ChDof genes could be divided into eight groups, and the members of the same group had similar motif arrangement and intron-exon structure. Promoter analysis showed that cis-acting elements responsive to abscisic acid, low temperature stress, and light were dominant. Transcriptome data revealed that most ChDof genes exhibited tissue-specific expression. Then, we performed by qRT-PCR to analyze the expression patterns of all 25 ChDof genes in fruit during storage. The results indicated that these genes exhibited different expression patterns, suggesting that they played an important role in fruit storage. Discussion: The results of this study provide a basis for further investigation of the biological function of Dof genes in C. humilis fruit.

PD-1 inhibitor causes pathological injury to multiple organs in a Lewis lung cancer mouse model.

Recently, immunotherapy has become one of the most promising strategies in the treatment of malignant tumors. However, nonspecific immune activation may lead to immunotherapy-related adverse effects (irAEs). IrAEs involve almost all organs and may be life-threatening. However, current research on irAEs is scarce, and knowledge regarding histopathology is insufficient. In the present study, after Lewis lung cancer mouse model formation, the experimental group mice were intraperitoneally injected with a programmed cell death protein 1 (PD-1) inhibitor. Hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and Masson's trichrome staining were used to evaluate the pathological characteristics of the heart, lungs, spleen, intestines, kidneys, and liver. Echocardiography was used to evaluate heart function. The results showed that one or more inflammatory cells were positively expressed in each organ in the PD-1 inhibitor group. Compared to the control group, Masson's trichrome staining showedincreased fibrosis of the heart, spleen, and kidney in the PD-1 inhibitor group, and echocardiography also showed impaired cardiac function in the PD-1 inhibitor group. Thus, the PD-1 inhibitor-induced inflammatory response may beimplicated in the impairment of multiple murine organs. This is the first study to describe the pathological changes in multiple organs caused by PD-1 inhibitors in a holistic form.

The chloroplast genome of Salix floderusii and characterization of chloroplast regulatory elements.

Salix floderusii is a rare alpine tree species in the Salix genus. Unfortunately, no extensive germplasm identification, molecular phylogeny, and chloroplast genomics of this plant have been conducted. We sequenced the chloroplast (cp) genome of S. floderusii for the first time using second-generation sequencing technology. The cp genome was 155,540 bp long, including a large single-copy region (LSC, 84,401 bp), a small single-copy region (SSC, 16,221 bp), and inverted repeat regions (IR, 54,918 bp). A total of 131 genes were identified, including 86 protein genes, 37 tRNA genes, and 8 rRNA genes. The S. floderusii cp genome contains 1 complement repeat, 24 forward repeats, 17 palindromic repeats, and 7 reverse repeats. Analysis of the IR borders showed that the IRa and IRb regions of S. floderusii and Salix caprea were shorter than those of Salix cinerea, which may affect plastome evolution. Furthermore, four highly variable regions were found, including the rpl22 coding region, psbM/trnD-GUC non-coding region, petA/psbJ non-coding region, and ycf1 coding region. These high variable regions can be used as candidate molecular markers and as a reference for identifying future Salix species. In addition, phylogenetic analysis indicated that the cp genome of S. floderusii is sister to Salix cupularis and belongs to the Subgenus Vetrix. Genes (Sf-trnI, Sf-PpsbA, aadA, Sf-TpsbA, Sf-trnA) obtained via cloning were inserted into the pBluescript II SK (+) to yield the cp expression vectors, which harbored the selectable marker gene aadA. The results of a spectinomycin resistance test indicated that the cp expression vector had been successfully constructed. Moreover, the aadA gene was efficiently expressed under the regulation of predicted regulatory elements. The present study provides a solid foundation for establishing subsequent S. floderusii cp transformation systems and developing strategies for the genetic improvement of S. floderusii.

Clinical Evidence on the Use of Chinese Herbal Medicine for Acute Infectious Diseases: An Overview of Systematic Reviews.

Background: Acute infectious diseases constitute the most prevalent public health emergency (PHE) in China. Chinese herbal medicine (CHM) has long been used in the treatment of acute infections, but the overall evidence of its benefit and harm has not been comprehensively and systematically evaluated. Methods: We searched CBM, CNKI, Wanfang, PubMed, Cochrane Library, embase and preprint platforms to retrieve systematic reviews (SRs) on CHM for acute infectious. Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included. Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone. The AMSTAR 2 tool was used to assess the methodological quality of the retrieved studies. Information on interventions, control measures and outcomes of the included studies was extracted, and meta-analyses were qualitatively synthesized. Results: A total of 51 SRs and meta-analyses were eligible for this overview, including 19 for COVID-19, 11 for hand-foot-and-mouth disease, 8 for severe acute respiratory syndrome (SARS), 4 for tuberculosis, 3 for mumps, 2 for bacillary dysentery, 2 for H1N1 influenza and 2 for herpangina. Six systematic reviews were of high quality, all of which were on the use of CHM for COVID-19; 24 were of moderate quality; 10 were of low quality; and 11 were of very low quality. CHM appeared to have potential benefits in improving clinical symptoms and signs for most infections with an acceptable safety profile, and the clinical evidence of the benefits of CHM for acute respiratory infections such as COVID-19, SARS and H1N1 seems more sufficient than that for other acute infections. Conclusion: Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.

[Non-carcinogenic Risk Assessment of Cadmium Exposure Through Drinking Water in Chinese Residents Based on Age-stratification Weight].

Drinking water is an important cadmium (Cd) exposure pathway for residents in China. In order to quantitatively characterize the risk of cadmium exposure through drinking water, the Cd concentrations of three main drinking water types in China were collected via systematic literature review. The probability distribution of the exposure parameters was estimated using regression models. The non-carcinogenic risk of cadmium exposure to residents through drinking water was evaluated by Monte Carlo simulation. The results showed that significant differences were found among Cd contents in the three water types. The geometric mean of ρ(Cd) in tap water, untreated underground water, and surface water were (0.48±0.78), (1.07±1.82), and (1.04±1.38) µg·L-1, respectively. The non-carcinogenic risk assessment showed that the median of hazard quotients in all age groups and in the three water types were found to be less than 1. Compared with the exposure dose threshold recommended by the US EPA, the probabilities exceeding the threshold of underground water, surface source water, and tap water were 2.4%, 1.3%, and 1.0%, respectively. Children aged 6-8 had the greatest daily average dose of Cd, and the least exposure dose was found in the 15-17 age group. The result of Monte Carlo simulation based on age-stratification weight showed that people 18-44 years old accounted for 50.8% of the total number of people who exceeded the exposure threshold. In summary, the probability of noncarcinogenic risk caused by Cd exposure through drinking water of Chinese residents was relatively low. However, people in some sub-groups still had a relatively high probability of exceeding the exposure dose threshold. It is necessary to further strengthen the control of cadmium pollution in drinking water in order to reduce the health risk caused by cadmium exposure and ensure drinking water safety.

Xiaoketongbi Formula vs pregabalin for painful diabetic neuropathy: A single-center, randomized, single-blind, double-dummy, and parallel controlled clinical trial.

BACKGROUND: We assessed the efficacy and safety of the Xiaoketongbi Formula (XF) vs. pregabalin in patients with painful diabetic neuropathy (PDN). METHODS: Patients with PDN (n = 68) were included in a single-center, randomized, single-blind, double-dummy, parallel controlled clinical trial. The primary outcome was the change in the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN). Secondary outcomes evaluated included the reduction of BPI-DPN >50%, changes in the numeric rating scale-11 (NRS-11) score for pain, Daily Sleep Interference Diary (DSID), Patient Global Impression of Change (PGIC), nerve conduction velocity (NCV), and adverse events. RESULTS: After 10 weeks of treatment, the BPI-DPN score reduced from 42.44 ± 17.56 to 26.47 ± 22.22 and from 52.03 ± 14.30 to 37.85 ± 17.23 in the XF and pregabalin group (Ps < 0.001), respectively. The difference in the absolute change in BPI-DPN score between both groups was -1.79 (95% CI: -9.09, 5.50; p = 0.625). In the XF and pregabalin groups, 44.1% (15/34) and 20.6% (7/34) of patients reported a BPI-DPN reduction >50% (p = 0.038), respectively. There were no significant differences between groups in NRS-11 and DSID (Ps > 0.05). A significantly greater number of patients in the XF group felt "significantly improved" or "improved" than in the pregabalin group (35.3% (12/34) vs. 11.8% (4/34), p = 0.045). The absolute change in motor nerve conduction velocity of the right median nerve was significantly different between both groups (XF group 0.7 ± 2.3 vs. pregabalin group -2.2 ± 4.1, p = 0.004). No serious adverse events were reported in either group. CONCLUSIONS: XF is equivalent to pregabalin in reducing pain symptoms and improves the quality of life in patients with PDN. In addition, XF has the potential to improve nerve function by increasing NCV.

[Research Progress of Immune Checkpoint Inhibitor-associated Myocarditis].

Immune checkpoint inhibitors (ICIs) is a negative regulatory factor antibody, which activates T cells to play an anti-tumor effect in immunotherapy, and can also cause immune-related adverse responses, thereby inducing a series of immune related adverse events (irAEs). Among these irAEs, although the incidence of ICIs-related myocarditis is very low, the fatality rate is significantly higher than other adverse reactions, close to 50%. Clinicians should be vigilant when applying ICIs, but the pathogenesis of ICIs-related myocarditis is still unclear. This article combines the recent research results of ICIs to summarize the mechanism and clinical manifestations of ICIs-related myocarditis, so as to improve clinicians' understanding of the adverse reactions.
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Characterization of the complete chloroplast genome of Sanicula rubriflora F. Schmidt ex Maxim.

Sanicula rubriflora refers to a kind of edible wild herbs, which possesses reputed medicinal value. Chloroplasts (cp) is essential organelle in plant cells and has a genome that can be inherited autonomously. The complete chloroplast genome of S. rubriflora was assemble and annotated in the present study. It was a circular molecular genome with a size of 155,700 bp in length, which has a typical quadripartite structure. For instance, a large single-copy (LSC) of 85,979 bp and a pair of inverted repeats (IRs) of 26,333 bp were disconnected by a small single-copy (SSC) of 17,053bp. A total of 130 genes have been annotated, including 86 protein-coding genes (PCGs), 36 transfer RNA genes (tRNAs) and 8 ribosomal RNA genes (rRNAs). The total GC content of the complete chloroplast genome reached 37.9%. A maximum likelihood phylogenetic analysis with the reported chloroplast genomes revealed that S. rubriflora is most closely related to Saniculachinensis in the phylogenetic relationships.

Development of season-dependent land use regression models to estimate BC and PM1 exposure.

Reliable estimation of exposure to black carbon (BC) and sub-micrometer particles (PM1) within a city is challenging because of limited monitoring data as well as the lack of models suitable for assessing the intra-urban environment. In this study, to estimate exposure levels in the inner-city area, we developed land use regression (LUR) models for BC and PM1 based on specially designed mobile monitoring surveys conducted in 2019 and 2020 for three seasons. The daytime and nighttime LUR models were developed separately to capture additional details on the variation in pollutants. The results of mobile monitoring indicated similar temporal variation characteristics of BC and PM1. The mean concentrations of pollutants were higher in winter (BC: 4.72 µg/m3; PM1: 56.97 µg/m3) than in fall (BC: 3.74 µg/m3; PM1: 33.29 µg/m3) and summer (BC: 2.77 µg/m3; PM1: 27.04 µg/m3). For both BC and PM1, higher nighttime concentrations were found in winter and fall, whereas higher daytime concentrations were observed in the summer. A supervised forward stepwise regression method was used to select the predictors for the LUR models. The adjusted R2 of the LUR models for BC and PM1 ranged from 0.39 to 0.66 and 0.45 to 0.80, respectively. Traffic-related predictors were incorporated into all the models for BC. In contrast, more meteorology-related predictors were incorporated into the PM1 models. The concentration surface based on the LUR models was mapped at a spatial resolution of 100 m, and significant seasonal and diurnal trends were observed. PM1 was dominated by seasonal variations, whereas BC showed more spatial variation. In conclusion, the development of season-dependent diurnal LUR models based on mobile monitoring could provide a methodology for the estimation of exposure and screening of influencing factors of BC and PM1 in typical inner-city environments, and support pollution management.

[Probabilistic Risk Assessment of Arsenic Exposure Through Drinking Water Intake in Chinese Residents].

The total arsenic concentrations of the three main drinking water types in China were determined through a systematic literature review. The distribution models of drinking water exposure parameters for different age groups were obtained using the regression method. The carcinogenic and non-carcinogenic risks of different population groups caused by arsenic exposure through different drinking water types were evaluated by a probabilistic risk assessment. The results showed that the geometric mean of total arsenic content in all the drinking water samples in China was (13.0±38.1) µg·L-1. The highest arsenic content was found in the Inner Mongolia Autonomous Region, followed by Guangxi and Shanxi. Based on the relevant standards for drinking water quality, the probability exceeding the threshold value of groundwater and source water is 23.2% and 18.4%, respectively. According to the results of non-carcinogenic risk assessment, the probability of the residents drinking well water and surface water from the water source area exceeding the daily average exposure dose threshold was 24.0% and 19.5%, respectively. According to the carcinogenic risk assessment, the median of carcinogenic risk caused by arsenic in drinking water in China was 3.22×10-5, which is acceptable. The population group of 18-45 years old had the highest risk, and the median LCR was 1.37×10-5. There was still a certain probability that the LCR of drinking well water and surface water would exceed the acceptable risk level recommended by the US EPA. In conclusion, the potential health risks caused by arsenic exposure through drinking water intake exist among Chinese residents. Further control of the arsenic concentration in drinking water is required to reduce the health risk and improve the safety of drinking water. Meanwhile, it is suggested to strengthen the research on risk threshold to provide a scientific basis for the residents' health protection.