Palmitic acid induces ß-cell ferroptosis by activating ceramide signaling pathway.

Individuals with type 2 diabetes mellitus frequently display heightened levels of palmitic acid (PA) in their serum, which may lead to ß-cell damage. The involvement of ferroptosis, a form of oxidative cell death in lipotoxic ß-cell injury remains uncertain. Here, we have shown that PA induces intracellular lipid peroxidation, increases intracellular Fe2+ content and decreases intracellular glutathione peroxidase 4 (GPX4) expression. Furthermore, PA causes distinct changes in pancreatic islets and INS-1 cells, such as mitochondrial atrophy and increased membrane density. Furthermore, the presence of the ferroptosis inhibitor has a significant mitigating effect on PA-induced ß-cell damage. Mechanistically, PA increased ceramide content and c-Jun N-terminal kinase (JNK) phosphorylation. The ceramide synthase inhibitor effectively attenuated PA-induced ß-cell damage and GPX4/Fe2+ abnormalities, while inhibiting JNK phosphorylation. Additionally, the JNK inhibitor SP600125 improved PA-induced cell damage. In conclusion, by promoting ceramide synthesis, PA inhibited GPX4 expression and increased intracellular Fe2+ to induce ß-cell ferroptosis. Moreover, JNK may be a downstream mechanism of ceramide-triggered lipotoxic ferroptosis in ß-cells.

Surface Engineering of Cathode Materials: Enhancing the High Performance of Lithium-Ion Batteries.

The development and application of lithium-ion batteries present a dual global prospect of opportunity and challenge. With conventional energy sources facing reserve shortages and environmental issues, lithium-ion batteries have emerged as a transformative technology over the past decade, owing to their superior properties. They are poised for exponential growth in the realms of electric vehicles and energy storage. The cathode, a vital component of lithium-ion batteries, undergoes chemical and electrochemical reactions at its surface that directly impact the battery's energy density, lifespan, power output, and safety. Despite the increasing energy density of lithium-ion batteries, their cathodes commonly encounter surface-side reactions with the electrolyte and exhibit low conductivity, which hinder their utility in high-power and energy-storage applications. Surface engineering has emerged as a compelling strategy to address these challenges. This paper meticulously examines the principles and progress of surface engineering for cathode materials, providing insights into its potential advancements and charting its development trajectory for practical implementation.

Fine-tuning rice heading date through multiplex editing of the regulatory regions of key genes by CRISPR-Cas9.

Heading date (or flowering time) is a key agronomic trait that affects seasonal and regional adaption of rice cultivars. An unoptimized heading date can either not achieve a high yield or has a high risk of encountering abiotic stresses. There is a strong demand on the mild to moderate adjusting the heading date in breeding practice. Genome editing is a promising method which allows more precise and faster changing the heading date of rice. However, direct knock out of major genes involved in regulating heading date will not always achieve a new germplasm with expected heading date. It is still challenging to quantitatively adjust the heading date of elite cultivars with best adaption for broader region. In this study, we used a CRISPR-Cas9 based genome editing strategy called high-efficiency multiplex promoter-targeting (HMP) to generate novel alleles at cis-regulatory regions of three major heading date genes: Hd1, Ghd7 and DTH8. We achieved a series of germplasm with quantitative variations of heading date by editing promoter regions and adjusting the expression levels of these genes. We performed field trials to screen for the best adapted lines for different regions. We successfully expanded an elite cultivar Ningjing8 (NJ8) to a higher latitude region by selecting a line with a mild early heading phenotype that escaped from cold stress and achieved high yield potential. Our study demonstrates that HMP is a powerful tool for quantitatively regulating rice heading date and expanding elite cultivars to broader regions.

Bloodstream infection clusters for critically ill patients: analysis of two-center retrospective cohorts.

BACKGROUND: Bloodstream infections (BSI) are highly prevalent in hospitalized patients requiring intensive care. They are among the most serious infections and are highly associated with sepsis or septic shock, which can lead to prolonged hospital stays and high healthcare costs. This study aimed at establishing an easy-to-use nomogram for predicting the prognosis of patients with BSI. METHODS: In retrospective study, records of patients with BSI admitted to the intensive care unit (ICU) over the period from Jan 1st 2016 to Dec 31st 2021 were included. We used data from two different China hospitals as development cohort and validation cohort respectively. The demographic and clinical data of patients were collected. Based on all baseline data, k-means algorithm was applied to discover the groups of BSI phenotypes with different prognostic outcomes, which was confirmed by Kaplan-Meier analysis and compared using log-rank tests. Univariate Cox regression analyses were used to estimate the risk of clusters. Random forest was used to identified discriminative predictors in clusters, which were utilized to construct nomogram based on multivariable logistic regression in the discovery cohort. For easy clinical applications, we developed a bloodstream infections clustering (BSIC) score according to the nomogram. The results were validated in the validation cohort over a similar period. RESULTS: A total of 360 patients in the discovery cohort and 310 patients in the validation cohort were included in statistical analyses. Based on baseline variables, two distinct clusters with differing prognostic outcomes were identified in the discovery cohort. Population in cluster 1 was 211 with a ICU mortality of 17.1%, while population in cluster 2 was 149 with an ICU mortality of 41.6% (p < 0.001). The survival analysis also revealed a higher risk of death for cluster 2 when compared with cluster 1 (hazard ratio: 2.31 [95% CI, 1.53 to 3.51], p < 0.001), which was confirmed in validation cohort. Four independent predictors (vasoconstrictor use before BSI, mechanical ventilation (MV) before BSI, Deep vein catheterization (DVC) before BSI, and antibiotic use before BSI) were identified and used to develop a nomogram. The nomogram and BSIC score showed good discrimination with AUC of 0.96. CONCLUSION: The developed score has potential applications in the identification of high-risk critically ill BSI patients.

Myocardial strain is regulated by cardiac preload in the early stage of sepsis.

BACKGROUND: Owing to a lack of data, this study aimed to explore the effect of cardiac preload on myocardial strain in patients with sepsis. METHODS: A total of 70 patients with sepsis in intensive care unit (ICU) of a tertiary teaching hospital in China from January 2018 to July 2019 and underwent transthoracic echocardiography were enrolled. Echocardiographic data were recorded at ICU admission and 24 h later. Patients were assigned to low left ventricular end-diastolic volume index (LVEDVI) and normal LVEDVI groups. We assessed the impact of preload on myocardial strain between the groups and analyzed the correlation of echocardiographic parameters under different preload conditions. RESULTS: Thirty-seven patients (53%) had a low LVEDVI and 33 (47%) a normal LVEDVI. Those in the low LVEDVI group had a faster heart rate (121.7 vs. 95.3, p < 0.001) and required a greater degree of fluid infusion (3.67 L vs. 2.62 L, P = 0.019). The left ventricular global strain (LVGLS) (-8.60% vs. -10.80%, p = 0.001), left ventricular global circumferential strain (LVGCS) (-13.83% vs. -18.26%, p = 0.006), and right ventricular global longitudinal strain (RVGLS) (-6.9% vs. -10.60%, p = 0.001) showed significant improvements in the low LVEDVI group after fluid resuscitation. However, fluid resuscitation resulted in a significantly increased cardiac afterload value (1172.00 vs. 1487.00, p = 0.009) only in the normal LVEDVI group. Multivariate backward linear regression showed that LVEDVI changes were independently associated with myocardial strain-related improvements during fluid resuscitation. The baseline LVEDVI was significantly negatively correlated with the LVGLS and RVGLS (r = -0.44 and - 0.39, respectively) but not LVGCS. LVEDVI increases during fluid resuscitation were associated with improvements in the myocardial strain degree. CONCLUSIONS: Myocardial strain alterations were significantly influenced by the cardiac preload during fluid resuscitation in sepsis.

Development of a TLR-Based Model That Can Predict Prognosis, Tumor Microenvironment, and Drug Response for Esophageal Squamous Cell Carcinoma.

The toll-like receptor (TLR) family is an important class of proteins involved in the immune response. However, little is known about the association between TLRs and Esophageal squamous cell cancer (ESCC). We explored differentially expressed genes (DEGs) between ESCC and esophagus tissues in TCGA and GTEx database. By taking the intersection with TLR gene set and using univariate Cox analysis and multivariate Cox regression analysis to discriminate the hub genes, we created a TLR-prognostic model. Our model separated patients with ESCC into high- and low-risk score (RS) groups. Prognostic analysis was performed with Kaplan-Meier curves. The two groups were also compared regarding tumor immune microenvironment and drug sensitivity. Six hub genes (including CD36, LGR4, MAP2K3, NINJ1, PIK3R1, and TRAF3) were screened to construct a TLR-prognostic model. High-RS group had a worse survival (p < 0.01), lower immune checkpoint expression (p < 0.05), immune cell abundance (p < 0.05) and decreased sensitivity to Epirubicin (p < 0.001), 5-fluorouracil (p < 0.0001), Sorafenib (p < 0.01) and Oxaliplatin (p < 0.05). We constructed a TLR-based model, which could be used to assess the prognosis of patients with ESCC, provide new insights into drug treatment for ESCC patients and investigate the TME and drug response.

Feasibility of repairing skin defects by VEGF165 gene-modified iPS-HFSCs seeded on a 3D printed scaffold containing astragalus polysaccharide.

The preparation of biodegradable scaffolds loaded with cells and cytokine is a feature of tissue-engineered skin. IPSCs-based tissue-engineered skin treatment for wound repair is worth exploring. Healthy human skin fibroblasts were collected and reprogrammed into iPSCs. After gene modification and induction, CK19+ /Integrinß1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP were obtained and identified by a combination of immunofluorescence and RT-qPCR. Astragalus polysaccharide-containing 3D printed degradable scaffolds were prepared and co-cultured with VEGF165 gene-modified iPS-HFSCsGFP , and the biocompatibility and spatial structure of the tissue-engineered skin was analysed by cell counting kit-8 (CCK8) assay and scanning electron microscopy. Finally, the tissue-engineered skin was transplanted onto the dorsal trauma of nude mice, and the effect of tissue-engineered skin on the regenerative repair of total skin defects was evaluated by a combination of histology, immunohistochemistry, immunofluorescence, RT-qPCR, and in vivo three-dimensional reconstruction under two-photon microscopy. CK19+ /Integrinß1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP , close to the morphology and phenotype of human-derived hair follicle stem cells, were obtained. The surface of the prepared 3D printed degradable scaffold containing 200 µg/mL astragalus polysaccharide was enriched with honeycomb-like meshwork, which was more conducive to the proliferation of the resulting cells. After tissue-engineered skin transplantation, combined assays showed that it promoted early vascularization, collagen and hair follicle regeneration and accelerated wound repair. VEGF165 gene-modified iPS-HFSCsGFP compounded with 3D printed degradable scaffolds containing 200 µg/mL astragalus polysaccharide can directly and indirectly participate in vascular, collagen, and hair follicle regeneration in the skin, achieving more complete structural and functional skin regenerative repair.

Genome-wide identification and expression analyses of the pectate lyase (PL) gene family in Fragaria vesca.

BACKGROUND: Pectate lyase (PL, EC 4.2.2.2), as an endo-acting depolymerizing enzyme, cleaves α-1,4-glycosidic linkages in esterified pectin and involves a broad range of cell wall modifications. However, the knowledge concerning the genome-wide analysis of the PL gene family in Fragaria vesca has not been thoroughly elucidated. RESULTS: In this study, sixteen PLs members in F. vesca were identified based on a genome-wide investigation. Substantial divergences existed among FvePLs in gene duplication, cis-acting elements, and tissue expression patterns. Four clusters were classified according to phylogenetic analysis. FvePL6, 8 and 13 in cluster II significantly contributed to the significant expansions during evolution by comparing orthologous PL genes from Malus domestica, Solanum lycopersicum, Arabidopsis thaliana, and Fragaria×ananassa. The cis-acting elements implicated in the abscisic acid signaling pathway were abundant in the regions of FvePLs promoters. The RNA-seq data and in situ hybridization revealed that FvePL1, 4, and 7 exhibited maximum expression in fruits at twenty days after pollination, whereas FvePL8 and FvePL13 were preferentially and prominently expressed in mature anthers and pollens. Additionally, the co-expression networks displayed that FvePLs had tight correlations with transcription factors and genes implicated in plant development, abiotic/biotic stresses, ions/Ca2+, and hormones, suggesting the potential roles of FvePLs during strawberry development. Besides, histological observations suggested that FvePL1, 4 and 7 enhanced cell division and expansion of the cortex, thus negatively influencing fruit firmness. Finally, FvePL1-RNAi reduced leaf size, altered petal architectures, disrupted normal pollen development, and rendered partial male sterility. CONCLUSION: These results provide valuable information for characterizing the evolution, expansion, expression patterns and functional analysis, which help to understand the molecular mechanisms of the FvePLs in the development of strawberries.

Streptomyces chengmaiensis sp. nov., isolated from the stem of a mangrove plant in Hainan.

A novel Streptomyces strain, designated as HNM0663T, was isolated from the stem of a mangrove plant (Avicennia marina) collected from the coast of Chengmai city, Hainan Island, PR China. On the basis of the alignment of 16S rRNA gene sequences, strain HNM0663T was closely related to Streptomyces lichenis LCR6-01T (98.67 %), Streptomyces nanningensis YIM 33098T (98.12 %) and Streptomyces palmae CMU-AB204T (97.93 %). Genome-based comparisons showed that strain HNM0663T was distinguished from its closest related species with 80.3 % average nucleotide identity and 20.2 % digital DNA-DNA hybridization values. The main cellular fatty acids were iso-C16 : 0, iso-C15 : 0 and anteiso-C15 : 0. The main menaquinones were MK-9 (H6), MK-9 (H4) and MK-8 (H4). The predominant phospholipids contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylcholine. Based on these polyphasic taxonomy results, strain HNM0663T should represent a novel Streptomyces species, for which the name Streptomyces chengmaiensis sp. nov. is proposed. The type strain is HNM 0663T (=CCTCC AA 2019075T=LMG 31909T).

Composition, functional, and niche differentiation of fungal communities in the rhizosphere and root endosphere of Cinnamomum migao in southwestern China.

AIMS: Roots are key parts of plant material circulation and energy flow, creating two distinct niches for the plant microbiome, such as the rhizosphere and root endosphere, which interact to maintain plant growth and health. In this study, two niches of plant rhizosphere and root endosphere were selected to study the composition and differences of fungi communities in order to better understand how differences in the structure and function of plant fungi communities affect plant health. METHODS AND RESULTS: The community structure, diversity, and ecological function of fungi in the rhizosphere and root endosphere of Cinnamomum migao were studied using high-throughput sequencing techniques, traditional culture methods, and the FUNGuild database. The results of the analysis of alpha diversity showed that the diversity of rhizosphere fungal communities in C. migao was much higher than that of root endosphere communities. Some similarities and differences were noted between the two niche fungal communities, and some fungi had niche preferences. Functional prediction results demonstrated that fungi in the rhizosphere and root endosphere adopt multiple trophic modes, mostly saprophytic fungi. CONCLUSIONS: This study provided a basis for an in-depth understanding of the structural variation, niche differentiation, and function of plant root-related fungal microbiota. We believe that it could provide guidance on the subsequent development of beneficial fungi.

Physcomitrium patens CAD1 has distinct roles in growth and resistance to biotic stress.

BACKGROUND: Physcomitrium patens provides an evolutionary link between green algae and vascular plants. Although the genome of P. patens includes orthologs of all the core lignin biosynthetic enzymes, the occurrence of lignin in moss is very controversial. Besides, little information is available about the lignin enzymes in moss to date. For example, cinnamyl alcohol dehydrogenase (CAD) is a crucial enzyme that catalyzes the last step of the lignin biosynthetic pathway, suggesting an ideal way to study the evolutionary process. By investigating the functions of CAD in evolution, this study will elucidate the evolutionary roles of lignin-like in the early stage of land colonization. RESULTS: CAD multigene family in P. patens is composed of four genes. The PpCADs contain a conserved glycine-rich domain to catalyze NADPH-dependent reduction to their corresponding alcohols, indicating that PpCADs have the potential to synthesize monolignols by bioinformatics analysis. Even though PpCAD1 could produce lignin in theory, no conventional monomer was detected in the cell wall or cytoplasm of PpCAD1_OE plants. However, the phenylpropanoids were promoted in PpCAD1_OE transformants to modify gametophore architecture and development, making the distribution of phyllids more scarcity and the moss colony more giant, possibly due to the enhanced expression of the AUX-IAA family. The transcripts of at least one gene encoding the enzyme in the lignin biosynthetic pathway were increased in PpCAD1_OE plants. In addition, the PpCAD1_OE gametophore inhibited the Botrytis cinerea assault mainly by enhanced phenylpropanoids in the cell wall instead of influencing transcripts of defense genes pathogenesis-related 10 (PR10) and nonexpresser of PR genes 1 (NPR1). Likewise, ectopic expression of PpCAD1 in Arabidopsis led to a significant increase in lignin content, exhibiting chunky roots, robust seedlings, advanced flowering, and efficient resistance against pathogens. CONCLUSION: PpCAD occurs in more than one copy, suggesting functional divergence in the ancestral plant. PpCAD1 catalyzes monolignol biosynthesis and has homologous functions with vascular plants. Despite no detected conventional monolignol, the increased phenylpropanoids in the PpCAD1_OE gametophore, possibly intermediate metabolites in the lignin pathway, had conserved functions during the evolution of terrestrial plants. The results inferred that the lignin enzyme of the early non-vascular plant played roles in stem elongation and resistance against pathogens of P. patens during the conquest of land.

Gibberellin and auxin signaling genes RGA1 and ARF8 repress accessory fruit initiation in diploid strawberry.

Unlike ovary-derived botanical fruits, strawberry (Fragaria x ananassa) is an accessory fruit derived from the receptacle, the stem tip subtending floral organs. Although both botanical and accessory fruits initiate development in response to auxin and gibberellic acid (GA) released from seeds, the downstream auxin and GA signaling mechanisms underlying accessory fruit development are presently unknown. We characterized GA and auxin signaling mutants in wild strawberry (Fragaria vesca) during early stage fruit development. While mutations in FveRGA1 and FveARF8 both led to the development of larger fruit, only mutations in FveRGA1 caused parthenocarpic fruit formation, suggesting FveRGA1 is a key regulator of fruit set. FveRGA1 mediated fertilization-induced GA signaling during accessory fruit initiation by repressing the expression of cell division and expansion genes and showed direct protein-protein interaction with FveARF8. Further, fvearf8 mutant fruits exhibited an enhanced response to auxin or GA application, and the increased response to GA was due to increased expression of FveGID1c coding for a putative GA receptor. The work reveals a crosstalk mechanism between FveARF8 in auxin signaling and FveGID1c in GA signaling. Together, our work provides functional insights into hormone signaling in an accessory fruit, broadens our understanding of fruit initiation in different fruit types, and lays the groundwork for future improvement of strawberry fruit productivity and quality.

A method for scattering angle calibration in the rainbow region using a droplet stream.

Accurate quantification of scattering angle versus detector pixel strongly determines the measurement accuracy of rainbow refractometry. This is an emerging measurement technique operating at backscatter angles and characterizing droplets or complex droplets in terms of size and refractive index. A novel method for calibration of the rainbow scattering angle using a monodisperse droplet stream is introduced and the achievable accuracy is estimated. The assumption of a linear pixel-to-angle relation is derived, and a calibration procedure is proposed based on global fit of calibration data to the theoretically known rainbow signal. The accuracy of this method was examined by simulations and experiments, where the uncertainties of a priori parameters of droplets were also considered and validated using shadowgraphy as a ground truth. The results confirm the feasibility of this method with a maximum absolute error of 0.032°and 3.9E-5°/pixel respectively for the intercept and slope of the linear relationship. These values translate into maximum uncertainties in diameter and refractive index of approx. 0.67% and 2.8 × 10-4.

Short-term ambient air pollution exposure and adult primary insomnia outpatient visits in Chongqing, China: A time-series analysis.

Growing evidence suggest that air pollutants can be associated with sleep disorders. However, no study has explored the association of short-term air pollution exposure with primary insomnia, a specific type of sleep disorders. To evaluate the correlation of short-term air pollution exposure with adult primary insomnia outpatient visits in Chongqing, China, we collected data of adult primary insomnia outpatient visits and air pollutants' concentrations between 2013 and 2019 and the associations were estimated with single-day lags as well as moving average lags using a generalized additive model. Totally, 23,919 outpatient visits for adult primary insomnia were identified. The daily data of adult insomnia outpatient visits, air pollutants (NO2, CO, SO2, O3, PM10 and PM2.5) and meteorological conditions (daily mean temperature and relative humidity) were gathered. Short-term exposure to multiple air pollutants, especially NO2 and SO2, was associated with adult primary insomnia visits. A 10 µg/m3 increase in NO2 and SO2 at lag 05 corresponded to increased primary insomnia outpatient visits 3.87% (95% CI: 1.50%-6.24%) and 7.22% (95% CI: 2.10%-12.35%), respectively. Moreover, stronger links were presented in females and cool seasons for NO2 while in the elderly for SO2. Collectively, this time-series study suggested that short-term exposure to air pollutants, especially to NO2 and SO2, was associated with higher risk of adult primary insomnia outpatient visits, and such association could to be sex-, age-, and season-modified.

Association between short-term ambient nitrogen dioxide and type 2 diabetes outpatient visits: A large hospital-based study.

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO2) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 µg/m3 increase of NO2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO2. Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO2 on the burden of T2DM, especially for those vulnerable groups.

Rapid reduction in triglyceride levels by therapeutic plasma exchange in patients with hypertriglyceridemic pancreatitis.

OBJECTIVE: To investigate the effect of therapeutic plasma exchange (TPE) on lowering triglyceride (TG) levels in patients with hypertriglyceridemic pancreatitis (HLAP). METHODS: The TG-lowering in patients with HLAP was compared between the TPE group and conservative treatment group (non-TPE). The primary outcome was TG reduction to less than 500 mg/dL within 48 hours. RESULTS: The primary outcome was significantly correlated with TPE (univariate analysis odds ratio [OR] 2.74; 95% confidence interval [CI] 1.30-5.79, P = .008; multivariate analysis OR 3.03; 95% CI 1.28-7.19, P = .012). At 24 and 48 hours, conservative treatment resulted in a 48.24% and 70.44% reduction in TG, while TPE resulted in a 70.91% and 76.39% reduction in TG, respectively. A more rapid decrease of in TGs in a short period was clearly associated with TPE (P < .001 for interaction). After 72 hours, the TGs decreased by approximately 77% in both groups, with no significant difference (P = .563). There was no difference between groups in clinical outcomes over the acute time period or over the longer term. CONCLUSIONS: In patients with HLAP, TPE resulted in a short-term and rapid reduction in plasma TG concentrations, with no significant advantage over non-TPE after 72 hours.

First-line or second-line PD-1 inhibition in advanced oesophageal squamous cell carcinoma: A prospective, multicentre, registry study.

WHAT IS KNOWN AND OBJECTIVE: First-line and second-line immunotherapy with programmed death-1 (PD-1) inhibitors both improve overall survival in patients with advanced oesophageal squamous cell cancer (ESCC). This study explored survival differences between first-line and second-line PD-1 inhibition in advanced ESCC. METHODS: This registry study included 167 patients with advanced ESCC who were exposed to PD-1 inhibitors in either a first-line or a second-line setting between 15 January 2019 and 31 October 2020. The primary endpoint was overall survival, and secondary endpoints included overall tumour response, progression-free survival (PFS) and PFS2. A propensity score-matching (PSM) analysis was performed using the nearest-neighbour method. RESULTS AND DISCUSSION: Sixty-one patients started first-line treatment with chemotherapy and a PD-1 inhibitor (Group 1), while 106 started chemotherapy as the first-line choice and received a PD-1 inhibitor as the second-line choice (Group 2). The median PFS was 7.1 months in Group 1 and 4.1 months in Group 2 (log-rank p = 0.001). The median PFS2 was 7.1 months in Group 1 and 7.4 months in Group 2 (log-rank p = 0.4). Before PSM, the median overall survival was 13.5 months in Group 1 and 14.1 months in Group 2 (log-rank p = 0.9), and the sensitivity analysis showed consistent results (14.0 vs. 14.1 months). After PSM, the median overall survival rates for Group 1 (n = 61) and Group 2 (n = 61) were 13.5 and 13.1 months (log-rank p = 0.7) respectively. WHAT IS NEW AND CONCLUSION: In this study, patients with advanced ESCC who received first-line or second-line PD-1 inhibitors seemed to have comparable overall survival.

New Diterpene and Indole Alkaloid Analogs from the Streptomyces malaysiensis SCSIO 41397.

One new cyclooctatin-type diterpenoid, 15-hydroxycyclooctatin (1), and one new indole alkaloid, streptoprenylindole D (3), along with 9 known compounds, were isolated from the Streptomyces malaysiensis SCSIO 41397. Their structures were established on the basis of spectroscopic analysis, optical rotation, and by a comparison with data from the literature. All isolated compounds were evaluated for their antibacterial (MRSA), antitumor (22Rv1 and PC-3) and antiviral (HSV-1/2) activities. According to the analysis of biological gene clusters in the whole genome, we preliminarily locate the gene clusters related to the synthesis of 15-hydroxycyclooctatin (1).

Transcriptome analysis of Cinnamomum migao seed germination in medicinal plants of Southwest China.

BACKGROUND: Cinnamomum migao is an endangered evergreen woody plant species endemic to China. Its fruit is used as a traditional medicine by the Miao nationality of China and has a high commercial value. However, its seed germination rate is extremely low under natural and artificial conditions. As the foundation of plant propagation, seed germination involves a series of physiological, cellular, and molecular changes; however, the molecular events and systematic changes occurring during C. migao seed germination remain unclear. RESULTS: In this study, combined with the changes in physiological indexes and transcription levels, we revealed the regulation characteristics of cell structures, storage substances, and antioxidant capacity during seed germination. Electron microscopy analysis revealed that abundant smooth and full oil bodies were present in the cotyledons of the seeds. With seed germination, oil bodies and other substances gradually degraded to supply energy; this was consistent with the content of storage substances. In parallel to electron microscopy and physiological analyses, transcriptome analysis showed that 80-90 % of differentially expressed genes (DEGs) appeared after seed imbibition, reflecting important development and physiological changes. The unigenes involved in material metabolism (glycerolipid metabolism, fatty acid degradation, and starch and sucrose metabolism) and energy supply pathways (pentose phosphate pathway, glycolysis pathway, pyruvate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation) were differentially expressed in the four germination stages. Among these DEGs, a small number of genes in the energy supply pathway at the initial stage of germination maintained high level of expression to maintain seed vigor and germination ability. Genes involved in lipid metabolism were firstly activated at a large scale in the LK (seed coat fissure) stage, and then genes involved in carbohydrates (CHO) metabolism were activated, which had their own species specificity. CONCLUSIONS: Our study revealed the transcriptional levels of genes and the sequence of their corresponding metabolic pathways during seed germination. The changes in cell structure and physiological indexes also confirmed these events. Our findings provide a foundation for determining the molecular mechanisms underlying seed germination.

Effects of rhizosphere fungi on the chemical composition of fruits of the medicinal plant Cinnamomum migao endemic to southwestern China.

BACKGROUND: This study examined how rhizosphere fungi influence the accumulation of chemical components in fruits of a small population species of Cinnamomum migao. RESULTS: Ascomycota and Basidiomycota were dominant in the rhizosphere fungal community of C. migao. Pestalotiopsis and Gibellulopsis were associated with α-Terpineol and sabinene content, and Gibellulopsis was associated with crude fat and carbohydrate content. There were significant differences in rhizosphere fungal populations between watersheds, and there was no obvious change between fruiting periods. Gibberella, Ilyonectria, Micropsalliota, and Geminibasidium promoted sabinene accumulation, and Clitocybula promoted α-Terpineol accumulation. CONCLUSION: The climate-related differentiation of rhizosphere fungal communities in watershed areas is the main driver of the chemical composition of C. migao fruit. The control of the production of biologically active compounds by the rhizosphere fungal community provides new opportunities to increase the industrial and medicinal value of the fruit of C. migao.