An alternative fully human anti-BCMA CAR-T shows response for relapsed or refractory multiple myeloma with anti-BCMA CAR-T exposures previously.

Chimeric antigen receptor T (CAR-T) cells therapy has made remarkable progress in relapsed/refractory multiple myeloma (R/R MM) treatment. Unfortunately, patients still eventually experience disease progression or relapse even after receiving anti-BCMA CAR-T therapy. At present, there are limited data on available treatment options for patients who have progressed on anti-BCMA CAR-T therapy. In this study, we evaluated the safety and efficacy of fully human anti-BCMA CAR-T (HRC0202) in seven R/R MM patients who were previously exposed to anti-BCMA CAR-T therapy. Three patients received 6.0 × 106 CAR+T cells/kg, one patient received 10.0 × 106 CAR+T cells/kg and three patients received 15.0 × 106 CAR+T cells/kg. Cytokine release syndrome (CRS) of grades 1-2 occurred in three patients (42.9%) and grade ≥3 in two patients (28.6%). Immune effector cell-associated neurotoxic syndrome (ICANS) was not observed in any of the patients. The best overall response rate (ORR) was 71.4% (5/7), with a stringent complete response/complete response (sCR/CR) achieved in three patients. The median progression-free survival (PFS) was 269 days, and median overall survival (OS) for all patients was not reached. The median peak concentration (Cmax) of HRC0202 was 30117.70 (range, 6084.35-147415.10) copies/µg DNA. This study indicated that fully human anti-BCMA CAR-T (HRC0202) is a promising treatment for R/R MM patients who relapsed or refractory from prior anti-BCMA CAR-T infusion.

Integrated Metabolomic and Transcriptomic Analyses Reveal the Potential Regulation of Flavonoids in the Production of Embryogenic Cultures during Early Somatic Embryogenesis of Longan (Dimocarpus longan Lour.).

Embryogenic cultures of longan (Dimocarpus longan Lour.) contain various metabolites with pharmacological properties that may function in the regulation of somatic embryogenesis (SE). In this study, based on widely targeted metabolomics, 501 metabolites were obtained from the embryogenic calli, incomplete compact proembryogenic cultures, and globular embryos during early SE of longan, among which 41 flavonoids were differentially accumulated during the SE. Using RNA sequencing, 36 flavonoid-biosynthesis-related genes and 43 MYB and 52 bHLH transcription factors were identified as differentially expressed genes. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the flavonoid metabolism-related pathways were significantly enriched during the early SE. These results suggested that the changes in flavonoid levels in the embryogenic cultures of longan were mediated by MYBs and bHLHs via regulating flavonoid-biosynthesis-related genes, thus potentially regulating early SE. The identified metabolites in the embryogenic cultures of longan can be used to develop pharmaceutical ingredients.

Characteristics of antibiotic resistance genes and microbial community distribution in Wanfeng Lake, upper Pearl River, China.

Wanfeng Lake, a highland lake in the upper part of the Pearl River Basin, China, has long been disturbed by aquaculture and human activities, resulting in the accumulation of antibiotics and antibiotic resistance genes (ARGs), which pose a major threat to humans and animals. In this study, 20 antibiotics, 9 ARGs, 2 mobile genetic elements (intl1 and intl2), and microbial community structure were investigated in Wanfeng Lake. The results of the study showed that the total concentration of antibiotics in surface water was 372.72 ng/L, with ofloxacin (OFX) having the highest concentration (169.48 ng/L), posing a high ecological risk to aquatic organisms. The total concentration of antibiotics in sediments was 235.86 ng/g, with flumequine (FLU) having the highest concentration (122.54 ng/g). This indicates that the main type of antibiotics in Wanfeng Lake are quinolones. QPCR analysis results of the relative abundance of ARGs in both surface water and sediments showed that sulfonamide resistance genes > macrolide resistance genes > tetracycline resistance genes > quinolone resistance genes, indicating that sulfonamide resistance genes were the dominant type. The metagenomic results showed that the predominant microorganisms in the sediment under the phylum level were Planctomycetes, Proteobacteria, Euryarchaeota, and Chloroflexi. Pearson's correlation analysis showed a significantly positive correlation between antibiotics and environmental factors with ARGs in Wanfeng Lake and a significant positive correlation between antibiotics and ARGs with microorganisms in sediments. This suggests that there is a potential pressure of antibiotics on ARGs, while microorganisms provide the driving force for the evolution and spread of ARGs. This study provides a basis for further research on the occurrence and spread of antibiotics and ARGs in Wanfeng Lake. A total of 14 antibiotics were detected in surface water and sediments. OFX poses a high ecological risk in all points of surface water. Antibiotics and ARGs were significantly positively correlated in Wanfeng Lake. Antibiotics and ARGs in sediments were positively correlated with microorganisms.

Pulmonary nocardiosis with bloodstream infection diagnosed by metagenomic next-generation sequencing in a kidney transplant recipient: A case report.

BACKGROUND: Pulmonary nocardiosis is difficult to diagnose by culture and other conventional testing, and is often associated with lethal disseminated infections. This difficulty poses a great challenge to the timeliness and accuracy of clinical detection, especially in susceptible immunosuppressed individuals. Metagenomic next-generation sequencing (mNGS) has transformed the conventional diagnosis pattern by providing a rapid and precise method to assess all microorganisms in a sample. CASE SUMMARY: A 45-year-old male was hospitalized for cough, chest tightness and fatigue for 3 consecutive days. He had received a kidney transplant 42 d prior to admission. No pathogens were detected at admission. Chest computed tomography showed nodules, streak shadows and fiber lesions in both lung lobes as well as right pleural effusion. Pulmonary tuberculosis with pleural effusion was highly suspected based on the symptoms, imaging and residence in a high tuberculosis-burden area. However, anti-tuberculosis treatment was ineffective, showing no improvement in computed tomography imaging. Pleural effusion and blood samples were subsequently sent for mNGS. The results indicated Nocardia farcinica as the major pathogen. After switching to sulphamethoxazole combined with minocycline for anti-nocardiosis treatment, the patient gradually improved and was finally discharged. CONCLUSION: A case of pulmonary nocardiosis with an accompanying bloodstream infection was diagnosed and promptly treated before the dissemination of the infection. This report emphasizes the value of mNGS in the diagnosis of nocardiosis. mNGS may be an effective method for facilitating early diagnosis and prompt treatment in infectious diseases, which overcomes the shortcomings of conventional testing.

DNA barcoding of Chinese snakes reveals hidden diversity and conservation needs.

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species-delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty-eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes.

Analysis of epidemiological trends of and associated factors for tooth loss among 35- to 44-year-old adults in Guangdong, Southern China, 1995-2015: a population-based cross-sectional survey.

BACKGROUND: Tooth loss is a known marker of oral and systemic health, but large-scale population-based and cross-sectional multi-year comparative studies on tooth loss have yet to be much studied in China. This study explores the changing trends in tooth loss status and the associated factors influencing the prevalence of tooth loss over the past two decades in Guangdong, Southern China. METHODS: Data from three cross-sectional, representative oral epidemiological surveys in Guangdong Province were analyzed, including 400 in 1995, 720 in 2005, and 288 in 2015, for a total of 1408 participants. Sample selection is based on the National Census of China published by the National Bureau of Statistics. In this study, each year, the number of missing teeth (MT) and the prevalence of tooth loss (MT > 0) were calculated. Basic demographic information, socioeconomic status, caries and periodontal status, personal lifestyle factors, and dental health care behaviors were analyzed by multivariate logistic regression to estimate their associations with tooth loss. Statistical significance was evaluated with 2-sided tests with a significance level of P < 0.05. RESULTS: This study found that the mean number of missing teeth and the prevalence of tooth loss among adults aged 35-44 years in Guangdong Province did not change significantly in the first decade (1995-2005) but decreased significantly in the second decade (2005-2015) (0.94 and 40.8% in 1995, 0.99 and 42.9% in 2005, and 0.63 and 33.3% in 2015, respectively). The mean number of MT by tooth position was highest for the first and second molars, and both were larger in the mandible than in the maxilla. In 1995, populations with low educational attainment and the presence of caries or periodontal pocket (periodontal probing depth ≥ 4 mm) were associated with a higher chance of MT > 0. In 2005, those with low educational attainment, the presence of caries, and 40-44 years old were associated with a higher chance of MT > 0. Moreover, in 2015, females, rural residents, and those with caries or periodontal pocket were associated with a higher chance of MT > 0. CONCLUSIONS: Although tooth retention has improved recently (2005-2015) and the preventive effect of education level on tooth loss has increased over time, efforts to prevent tooth loss in adults need to be strengthened. Particular attention should be given to preventive interventions for women, rural residents, and those suffering from caries or periodontal pocket.

Dihydroartemisinin elicits immunogenic death through ferroptosis-triggered ER stress and DNA damage for lung cancer immunotherapy.

BACKGROUND: The immunosuppressive microenvironment of lung cancer serves as an important endogenous contributor to treatment failure. The present study aimed to demonstrate the promotive effect of DHA on immunogenic cell death (ICD) in lung cancer as well as the mechanism. METHODS: The lewis lung cancer cells (LLC), A549 cells and LLC-bearing mice were applied as the lung cancer model. The apoptosis, ferroptosis assay, western blotting, immunofluorescent staining, qPCR, comet assay, flow cytometry, confocal microscopy, transmission electron microscopy and immunohistochemistry were conducted to analyze the functions and the underlying mechanism. RESULTS: An increased apoptosis rate and immunogenicity were detected in DHA-treated LLC and tumor grafts. Further findings showed DHA caused lipid peroxide (LPO) accumulation, thereby initiating ferroptosis. DHA stimulated cellular endoplasmic reticulum (ER) stress and DNA damage simultaneously. However, the ER stress and DNA damage induced by DHA could be abolished by ferroptosis inhibitors, whose immunogenicity enhancement was synchronously attenuated. In contrast, the addition of exogenous iron ions further improved the immunogenicity induced by DHA accompanied by enhanced ER stress and DNA damage. The enhanced immunogenicity could be abated by ER stress and DNA damage inhibitors as well. Finally, DHA activated immunocytes and exhibited excellent anti-cancer efficacy in LLC-bearing mice. CONCLUSIONS: In summary, the current study demonstrates that DHA triggers ferroptosis, facilitating the ICD of lung cancer thereupon. This work reveals for the first time the effect and underlying mechanism by which DHA induces ICD of cancer cells, providing novel insights into the regulation of the immune microenvironment for cancer immunotherapy by Chinese medicine phytopharmaceuticals.

Genome-wide analysis of the laccase gene family in wheat and relationship with arbuscular mycorrhizal colonization.

MAIN CONCLUSION: We identified 156 laccase genes belonging to 11 subfamilies in the wheat genome, and the natural variation of laccase genes significantly affected the development of wheat-arbuscular mycorrhizal symbiosis. Laccases (LACs) have a variety of functions in plant lignification, cell elongation and stress responses. This study aimed to reveal the phylogeny, chromosomal spatial distribution, coexpression and evolution of LAC genes in the wheat genome and to investigate the possible roles of LAC genes during arbuscular mycorrhizal (AM) symbiosis. The genomic characteristics of LAC genes were analyzed by using bioinformatics analysis methods, and the polymorphisms of LAC genes were analyzed by using a diverse wheat panel composed of 289 wheat cultivars. We identified 156 LAC genes belonging to 11 subfamilies in the wheat genome, and segmental duplication dominated the amplification of the LAC gene family in the wheat genome. LACs are dominantly located in the R2 region of wheat chromosomes. Some LACs are collinear with the characterized LACs in Arabidopsis thaliana or rice. A number of genes encoding transcription factors, kinases, and phosphatases were coexpressed with LAC genes in wheat. TaLACs may be potential targets for some miRNAs. Most TaLACs are mainly expressed in the roots and stems of plants. The expression of TaLACs could be regulated by the inoculation of Fusarium graminearum or AM fungi. The polymorphisms of TaLACs mainly accumulate by random drift instead of by selection. Through candidate gene association analysis, we found that the natural variations in TaLACs significantly affected root colonization by AM fungi. The present study provides useful information for further study of the biological functions of LAC genes in wheat, especially the roles of LAC genes during the development of AM symbiosis.

Study on microbes and antibiotic resistance genes in karst primitive mountain marshes - A case study of Niangniang Mountain in Guizhou, China.

Previous research on antibiotic resistance genes and microorganisms centered on those in urban sewage treatment plants, breeding farms, hospitals and others with serious antibiotic pollution. However, at present, there are evident proofs that antibiotic resistance genes (ARGs) indeed exist in a primitive environment hardly without any human's footprints. Accordingly, an original karst mountain swamp ecosystem in Niangniang Mountain, Guizhou, China, including herbaceous swamp, shrub swamp, sphagnum bog and forest swamp, was selected to analyze the physical and chemical parameters of sediments. Moreover, microbial compositions, functions, as well as their connections with ARGs were assayed and analyzed using metagenomic technology. The results showed that there was no significant difference in the dominant microorganisms and ARGs in the four marshes, in which the dominant bacteria phyla were Proteobacteria (37.82 %), Acidobacteriota (22.17 %) and Actinobacteriota (20.64 %); the dominant archaea Euryarchaeota. (1.00 %); and the dominant eukaryotes Ascomycota (0.07 %), with metabolism as their major functions. Based on the ARDB database, the number of ARGs annotated reached 209 including 30 subtypes, and the dominant ARGs were all Bacitracin resistance genes (bacA, 84.77 %). In terms of the diversity of microorganisms and ARGs, the herbaceous swamp ranked the top, and the shrub swamp were at the bottom. Correlation analysis between microorganisms and resistance genes showed that, apart from aac2ic, macB, smeE, tetQ, and tetL, other ARGs were positively correlated with microorganisms. Among them, baca coexisted with microorganisms. Pearson correlation analysis results showed that contrary to ARGs, microorganisms were more affected by environmental factors.

Light Quality Modulates Growth, Triggers Differential Accumulation of Phenolic Compounds, and Changes the Total Antioxidant Capacity in the Red Callus of Vitis davidii.

Light quality is one of the key elicitors that directly affect plant cell growth and biosynthesis of secondary metabolites. In this study, the red callus of spine grape was cultured under nine light qualities (namely, dark, white, red, yellow, blue, green, purple, warm-yellow, and warm-white light). The effects of different light qualities were studied on callus growth, accumulation of phenolic compounds, and total antioxidant capacity of the red callus of spine grape. The results showed that blue and purple light induced increased red coloration in the callus, whereas yellow light induced the greatest callus proliferation. Among all of the light quality treatments, darkness treatment downregulated the contents of phenolic compounds, whereas blue light was the treatment most conducive to the accumulation of total phenolics. White, blue, and purple light induced increased anthocyanin accumulation. Mixed-wavelength light was beneficial to the accumulation of flavonoids. Blue and purple light were conducive to the accumulation of proanthocyanidins. A further study showed that cyanidin 3-glucoside (Cy3G) and peonidin 3-glucoside (P3G) were the main anthocyanin components in the callus, and blue, purple, and white light treatments promoted their accumulation, whereas flavan-3-ols and flavonols were the main components of non-anthocyanin phenolics, and their accumulation changed in response to not only light quality but also culture duration. The total antioxidant capacity of the callus cultures changed significantly in response to different light qualities. These results will provide evidence for an abiotic elicitor strategy to stimulate callus growth and enhance the accumulation of the main phenolic compounds in the red callus of spine grape.

Genome-wide identification of miRNAs and targets associated with cell wall biosynthesis: Differential roles of dlo-miR397a and dlo-miR408-3p during early somatic embryogenesis in longan.

The dynamic alterations in cell wall (CW) biosynthesis play an essential role in physiological isolation during the plant somatic embryogenesis (SE). However, the mechanisms underlying the functions of cell wall-associated miRNAs (CW-miRNA) remain poorly understood in plant SE. Here, we have identified 36 distinct candidate miRNAs associated with CW biosynthesis from longan third-generation genome as well as miRNA transcriptome, and modified RLM-RACE validated four distinct miRNA, which specifically targeted four CW-related genes. More importantly, we found that the dlo-miR397a-antagomir significantly enhanced DlLAC7 expression and improved laccase activity. Interestingly, inhibition of dlo-miR397a increased CW lignin deposition and promoted the tightening of protodermal cell by miRNA-mimic technology during early SE. Moreover, overexpression of dlo-miR408-3p (dlo-miR408-3p-agomir) markedly decreased DlLAC12 expression. dlo-miR408-3p-agomir activated rapid cell division, thus promoting the globular embryo (GE) development, which might be due to high DNA synthesis activity in protoepidermal cells, rather than affecting lignin synthesis. The subcellular location also indicated that both DlLAC7 and DlLAC12 proteins were primarily localized in CW and regulated CW biosynthesis. Overall, our findings provided new insight on the molecular regulatory networks comprising various miRNAs associated with cell wall, and established that dlo-miR397a and dlo-miR408-3p played differential roles during early SE in longan. The findings also shed some light on the potential role of miRNA target DlLAC regulating in vivo embryonic development of plant.

The Dynamic Change in Fatty Acids during the Postharvest Process of Oolong Tea Production.

As important factors to oolong tea quality, the accumulation and dynamic change in aroma substances attracts great attention. The volatile composition of oolong tea is closely related to the precursor contents. Fatty acids (FAs) and their derivatives are basic components of oolong tea fragrance during the postharvest process. However, information about the precursors of FAs during the postharvest process of oolong tea production is rare. To investigate the transformation of fatty acids during the process of oolong tea production, gas chromatograph−flame ionization detection (GC-FID) was conducted to analyze the composition of FAs. The results show that the content of total polyunsaturated FAs initially increased and then decreased. Specifically, the contents of α-linolenic acid, linoleic acid and other representative substances decreased after the turn-over process of oolong tea production. The results of partial least squares discrimination analysis (PLS-DA) showed that five types of FAs were obviously impacted by the processing methods of oolong tea (VIP > 1.0). LOX (Lipoxygenase, EC 1.13.11.12) is considered one of the key rate-limiting enzymes of long-chain unsaturated FAs in the LOX-HPL (hydroperoxide lyase) pathway, and the mechanical wounding occurring during the postharvest process of oolong tea production greatly elevated the activity of LOX.

Genome-wide analyses of the Nodulin-like gene family in bread wheat revealed its potential roles during arbuscular mycorrhizal symbiosis.

Nodulin-like (NL) genes are involved in transporting of various substances and may play key roles during the establishment of symbiosis in legumes plants. However, basic biological information of NL genes in the wheat genome is still largely unknown. Here, we identified and characterized NL genes in wheat via integrating genomic information, collinearity analysis, co-expression network analysis (WGCNA) and transcriptome analysis. In addition, we analyzed the polymorphisms and the roles of NL genes during arbuscular mycorrhizal (AM) symbiosis using a large wheat panel consists of 259 wheat genotypes. We identified 181 NL genes in the wheat genome, which were classified into SWEET, Early Nodulin-Like (ENODL), Major Facilitator Superfamily-Nodulin (MFS), Vacuolar Iron Transporter (VIT) and Early nodulin 93 (ENOD93) subfamily. The expansion of NL genes was mainly driven by segmental duplication. The bHLH genes are potential unrecognized transcription factors regulating NL genes. Moreover, two NL genes were more sensitive than other NL genes to AM colonization. The polymorphisms of NL genes are mainly due to random drift, and the natural mutation of NL genes led to significant differences in the mycorrhizal dependence of wheat in phosphorus uptake. The results concluded that NL genes potentially play important roles during AM symbiosis with wheat.

[Characteristics and Risk Assessment of Antibiotic Contamination in Chishui River Basin, Guizhou Province, China].

To preliminarily explore the antibiotic concentration distribution characteristics of Guizhou Chishui River basin surface water and potential ecological risks, we used solid phase extraction liquid chromatography tandem mass spectrometry (SPE-HPLC- MS) to analyze 21 types of antibiotics in surface water samples. Twelve types of antibiotics were detected in the Chishui River basin surface water, and the total concentrations of ofloxacin, sulfadiazine, and trimethoprim ranged from ND-1166.97 ng·L-1, with a detection rate of 100%. On average, the highest concentration of the three types of antibiotics detected were ofloxacin (221.59 ng·L-1), tetracycline (13.18 ng·L-1), and sulfadiazine (4.11 ng·L-1), and the antibiotic concentration distribution showed the following order of characteristics:downstream (359.41 ng·L-1) > midstream(224.59 ng·L-1) > upstream (179.72 ng·L-1). The ecological environment risk assessment results indicated the largest risk for downstream W21, tetracycline, doxycycline, enrofloxacin, norfloxacin, and erythromycin. The risk quotient revealed that lincomycin had a medium-risk level, and ofloxacin had a high-risk level. This shows that antibiotics in the waters of the Chishui River basin may cause certain ecological risks.

The diversity of microbes and prediction of their functions in karst caves under the influence of human tourism activities-a case study of Zhijin Cave in Southwest China.

Microorganisms, sensitive to the surrounding environment changes, show how the cave environment can be impacted by human activities. Zhijin Cave, featured with the most well-developed karst landform in China, has been open to tourists for more than 30 years. This study explored the microbial diversity in a karst cave and the impacts of tourism activities on the microbial communities and the community structures of bacteria and archaea in three niches in Zhijin Cave, including the mixture of bacteria and cyanobacteria on the rock wall, the aquatic sediments, and the surface sediments, using 16S rRNA high-throughput sequencing technology. It was found that Actinobacteriota and Proteobacteria were the dominant bacteria in the cave and Crenarchaeota and Thermoplasmatota were the dominant archaea. The correlation between microorganisms and environmental variables in the cave showed that archaea were more affected by pH and ORP than bacteria and F-, Cl-, NO3-, and SO42- were all positively relevant to the distribution of most bacteria and archaea in the cave. PICRUSt's prediction of microbial functions also indicated that abundance of the bacteria's functions was higher than that of the archaea. The intention of this study was to improve the understanding, development, and protection of microbial resources in caves.

Metabolic Flow of C6 Volatile Compounds From LOX-HPL Pathway Based on Airflow During the Post-harvest Process of Oolong Tea.

Aroma is an essential quality indicator of oolong tea, a tea derived from the Camellia sinensis L. plant. Carboxylic 6 (C6) acids and their derivative esters are important components of fatty acid (FA)-derived volatiles in oolong tea. However, the formation and regulation mechanism of C6 acid during postharvest processing of oolong tea remains unclear. To gain better insight into the molecular and biochemical mechanisms of C6 compounds in oolong tea, a combined analysis of alcohol dehydrogenase (ADH) activity, CsADH2 key gene expression, and the FA-derived metabolome during postharvest processing of oolong tea was performed for the first time, complemented by CsHIP (hypoxia-induced protein conserved region) gene expression analysis. Volatile fatty acid derivative (VFAD)-targeted metabolomics analysis using headspace solid-phase microextraction-gas chromatography time-of-flight mass spectrometry (HS-SPEM-GC-TOF-MS) showed that the (Z)-3-hexen-1-ol content increased after each turnover, while the hexanoic acid content showed the opposite trend. The results further showed that both the ADH activity and CsADH gene expression level in oxygen-deficit-turnover tea leaves (ODT) were higher than those of oxygen-turnover tea leaves (OT). The C6-alcohol-derived ester content of OT was significantly higher than that of ODT, while C6-acid-derived ester content showed the opposite trend. Furthermore, the HIP gene family was screened and analyzed, showing that ODT treatment significantly promoted the upregulation of CsHIG4 and CsHIG6 gene expression. These results showed that the formation mechanism of oolong tea aroma quality is mediated by airflow in the lipoxygenase-hydroperoxide lyase (LOX-HPL) pathway, which provided a theoretical reference for future quality control in the postharvest processing of oolong tea.

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study.

Background: Sedatives are commonly used in patients with or at risk for acute respiratory distress syndrome (ARDS) during mechanical ventilation. To systematically compare the outcomes of sedation with midazolam, propofol, and dexmedetomidine in patients with or at risk for ARDS. Methods: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of sedatives and the associated outcomes from the MIMIC-III database and the eICU Collaborative Research database. We performed a systematic study with six cohorts to estimate the relative risks of outcomes among patients administered different sedatives. Propensity score matching was performed to generate a balanced 1:1 matched cohort and to identify potential prognostic factors. The outcomes included hospital mortality, duration of mechanical ventilation, length of intensive care unit stay, length of hospitalization, and likelihood of being discharged home. Results: We performed 60 calibrated analyses among all groups and outcomes with 17,410 eligible patients. Sedation with dexmedetomidine was associated with a lower in-hospital mortality rate than sedation with midazolam and propofol or sedation without dexmedetomidine (p < 0.001). When compared with no sedation, the use of midazolam, propofol or dexmedetomidine was associated with a longer ICU stay and longer hospitalization duration (p < 0.01). Patients treated with midazolam were relatively less likely to be discharged home (p < 0.05). Conclusion: Patients treated with dexmedetomidine had a reduced risk of mortality. These data suggest that dexmedetomidine may be the preferred sedative in patients with or at risk for ARDS.

[Methanotrophs bacteria in special environment: A review.] / ç‰¹æ®ŠçŽ¯å¢ƒä¸­ç”²çƒ·æ°§åŒ–èŒçš„ç ”ç©¶è¿›å±•.

Methanotrophs are important and unique prokaryotes widely distributed in the nature. They can oxidize methane and live at a moderate temperature in the conditions withpH=7. In addition, many methanotrophs have been isolated from various special conditions within a wide range of pH value and temperature, including acid sphagnum moss wetlands, acid forest soils, hot springs and high-temperature geothermal areas near volcanic craters, soda-saline lakes, and marine sediments. Here, we introduced the classification, properties and influencing factors of methanotrophs in these special conditions, and reviewed relevant technological researches and engineering applications, with the aim to facilitate further studies of natural biodiversity as well as global carbon and hydrogen cycles.

Foxo1 selectively regulates static mechanical pain by interacting with Nav1.7.

ABSTRACT: Mechanical allodynia is a debilitating condition for millions of patients with chronic pain. Mechanical allodynia can manifest in distinct forms, including brush-evoked dynamic and filament-evoked static allodynia. In the nervous system, the forkhead protein Foxo1 plays a critical role in neuronal structures and functions. However, the role of Foxo1 in the somatosensory signal remains unclear. Here, we found that Foxo1 selectively regulated static mechanical pain. Foxo1 knockdown decreased sensitivity to static mechanical stimuli in normal rats and attenuated static mechanical allodynia in rat models for neuropathic, inflammatory, and chemotherapy pain. Conversely, Foxo1 overexpression selectively enhanced sensitivity to static mechanical stimuli and provoked static mechanical allodynia. Furthermore, Foxo1 interacted with voltage-gated sodium Nav1.7 channels and increased the Nav1.7 current density by accelerating activation rather than by changing the expression of Nav1.7 in dorsal root ganglia neurons. In addition, the serum level of Foxo1 was found to be increased in chronic pain patients and to be positively correlated with the severity of chronic pain. Altogether, our findings suggest that serum Foxo1 level could be used as a biological marker for prediction and diagnosis of chronic pain. Moreover, selective blockade of Foxo1/Nav1.7 interaction may offer a new therapeutic approach in patients with mechanical pain.

Feasibility Analysis and Study Progress of Effect of Huangjingwan in Prevention and Treatment of Alzheimer's Disease / 中国实验方剂学杂志

Alzheimer's disease （AD） is a neurodegenerative disease that leads to progressive memory and cognitive impairment and behavioral disorders， which has seriously threatened the health of the majority of middle-aged and elderly people. Traditional Chinese medicine （TCM） believes that the basic pathogenesis of AD is deficiency of kidney-essence， blood stasis and meridian stagnation. In recent years， many studies have shown that TCM has obvious value and advantages in the prevention and treatment of AD by multi-target mechanism. Therefore， it is of great significance to screen out effective anti-AD drugs from TCM compound prescriptions. Huangjingwan， also known as Jiuzhuan Huangjingwan， has the effects in tonifying kidney-essence， activating blood and removing stasis， with a potential effect in preventing AD. In this article， the feasibility of Huangjingwan in the prevention and treatment of AD was analyzed and discussed from the perspective of TCM theory， the study results of Huangjingwan in the prevention and treatment of AD were summarized， and the mechanism of its action was analyzed from the perspective of pharmacological mechanism. Based on TCM theory， Huangjingwan has the effect of anti-AD. According to relevant findings， Huangjingwan has many targets， such as anti-oxidation， anti-inflammatory， decrease of the level of oxidative stress in brain， activation of Wnt/β-catenin signal transduction in brain， regulation of glycogen synthase kinase-3β （GSK-3β）， protein phosphatase 2A （PP2A） activity balance， reduction of amyloid β （Aβ） content and tau protein hyperphosphorylation in brain， so as to exert effects in improving neurological symptoms and increasing learning and memory ability， with an anti-AD neuroprotective function. This will provide new ideas for in-depth studies and clinical applications of Huangjingwan against AD.