Lrg1 silencing attenuates ischemia-reperfusion renal injury by regulating autophagy and apoptosis through the TGFß1- Smad1/5 signaling pathway.

BACKGROUND: Dysfunction in the processes of autophagy and apoptosis within renal tubular epithelial cells (RTEc) contributes to renal ischemia-reperfusion injury (IRI). However, the factors influencing this dysfunction remain unclear. Leucine-rich alpha-2-glycoprotein 1 (Lrg1) plays a role in the progression of diabetic nephropathy and kidney fibrosis by modulating the activin receptor-like kinase 1 (ALK1)-Smad1/5/8 and TGF-ß1/Smad3 pathways, respectively. Therefore, we aimed to investigate whether Lrg1 is involved in the pathological mechanisms of renal IRI and whether its effects are related to the dysregulation of autophagy and apoptosis in RTEc. METHODS: We conducted in vitro and in vivo experiments using CoCl2-induced hypoxic human kidney-2 (HK-2) cells and mice with renal IRI, respectively. Lrg1 was silenced using siRNA and lentiviral vectors in HK-2 cells and mouse kidneys. Rapamycin (Rapa) and methyladenine were applied to regulate autophagy in renal IRI models. RESULTS: Increased Lrg1 expression was observed in hypoxic HK-2 cells and in the kidneys of mice with renal IRI. Silencing of Lrg1 through siRNA and lentiviral approaches restored autophagy and suppressed apoptosis in CoCl2-induced hypoxic HK-2 cells and renal IRI models. Additionally, reduced Lrg1 expression alleviated kidney damage caused by renal IRI. The downregulation of Lrg1 expression restrained the TGFß-Smad1/5 signaling pathway in hypoxic-induced HK-2 cells and renal IRI by reducing ALK1 expression. Lastly, the enhancement of autophagy, achieved through Rapa treatment, provided protection against renal IRI in mice. CONCLUSIONS: Our findings suggest that Lrg1 silencing can be applied as a potential therapeutic target to inhibit the TGFß1-Smad1/5 pathway, thereby enhancing autophagy and decreasing apoptosis in patients with acute kidney injury.

Prognostic and predictive value of examined lymph node count in stage III colorectal cancer: a population based study.

BACKGROUND: The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood. METHODS: This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the "limma" package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration. RESULTS: Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment. CONCLUSIONS: The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value.

HRP-OG: Online Learning with Generative Feature Replay for Hypertension Risk Prediction in a Nonstationary Environment.

Hypertension is a major risk factor for many serious diseases. With the aging population and lifestyle changes, the incidence of hypertension continues to rise, imposing a significant medical cost burden on patients and severely affecting their quality of life. Early intervention can greatly reduce the prevalence of hypertension. Research on hypertension early warning models based on electronic health records (EHRs) is an important and effective method for achieving early hypertension warning. However, limited by the scarcity and imbalance of multivisit records, and the nonstationary characteristics of hypertension features, it is difficult to predict the probability of hypertension prevalence in a patient effectively. Therefore, this study proposes an online hypertension monitoring model (HRP-OG) based on reinforcement learning and generative feature replay. It transforms the hypertension prediction problem into a sequential decision problem, achieving risk prediction of hypertension for patients using multivisit records. Sensors embedded in medical devices and wearables continuously capture real-time physiological data such as blood pressure, heart rate, and activity levels, which are integrated into the EHR. The fit between the samples generated by the generator and the real visit data is evaluated using maximum likelihood estimation, which can reduce the adversarial discrepancy between the feature space of hypertension and incoming incremental data, and the model is updated online based on real-time data using generative feature replay. The incorporation of sensor data ensures that the model adapts dynamically to changes in the condition of patients, facilitating timely interventions. In this study, the publicly available MIMIC-III data are used for validation, and the experimental results demonstrate that compared to existing advanced methods, HRP-OG can effectively improve the accuracy of hypertension risk prediction for few-shot multivisit record in nonstationary environments.

Fluorinated Fullerenes as Electrolyte Additives for High Ionic Conductivity Lithium-Ion Batteries.

Currently, lithium-ion batteries have an increasingly urgent need for high-performance electrolytes, and additives are highly valued for their convenience and cost-effectiveness features. In this work, the feasibilities of fullerenes and fluorinated fullerenes as typical bis(fluorosulfonyl)imide/1,2-dimethoxymethane (LiFSI/DME) electrolyte additives are rationally evaluated based on density functional theory calculations and molecular dynamic simulations. Interestingly, electronic structures of C60, C60F2, C60F4, C60F6, 1-C60F8, and 2-C60F8 are found to be compatible with the properties required as additives. It is noted that that different numbers and positions of F atoms lead to changes in the deformation and electronic properties of fullerenes. The F atoms not only show strong covalent interactions with C cages, but also affect the C-C covalent interaction in C cages. In addition, molecular dynamic simulations unravel that the addition of trace amounts of C60F4, C60F6, and 2-C60F8 can effectively enhance the Li+ mobility in LiFSI/DME electrolytes. The results expand the range of applications for fullerenes and their derivatives and shed light on the research into novel additives for high-performance electrolytes.

Multisource Differential Fusion Driven Monocular Endoscope Hybrid 3-D Tracking for Advanced Endoscopic Navigation Surgery.

Surgical navigation systems involve various technologies of segmentation, calibration, registration, tracking, and visualization. These systems aim to superimpose multisource information in the surgical field and provide surgeons with a composite overlay (augmented-reality) view, improving the operative precision and experience. Surgical 3-D tracking is the key to build these systems. Unfortunately, surgical 3-D tracking is still a challenge to endoscopic and robotic navigation systems and easily gets trapped in image artifacts, tissue deformation, and inaccurate positional (e.g., electromagnetic) sensor measurements. This work explores a new monocular endoscope hybrid 3-D tracking method called spatially constrained adaptive differential evolution that combines two spatial constraints with observation-recall adaptive propagation and observation-based fitness computing for stochastic optimization. Specifically, we spatially constraint inaccurate electromagnetic sensor measurements to the centerline of anatomical tubular structures to keep them physically locating inside the tubes, as well as interpolate these measurements to reduce jitter errors for smooth 3-D tracking. We then propose observation-recall adaptive propagation with fitness computing to precisely fuse the constrained sensor measurements, preoperative images, and endoscopic video sequences for accurate hybrid 3-D tracking. Additionally, we also propose a new marker-free hybrid registration strategy to precisely align positional sensor measurements to preoperative images. Our new framework was evaluated on a large amount of clinical data acquired from various surgical endoscopic procedures, with the experimental results showing that it certainly outperforms current surgical 3-D approaches. In particular, the position and rotation errors were significantly reduced from (6.55, 11.4) to (3.02 mm, 8.54 °).

Neuroimmune regulation in the pancreas.

The pancreas exerts endocrine and exocrine functions in energy balance. The neural innervation and immune milieu are both crucial in supporting pancreatic homeostasis. The neuronal network connects the pancreas with the central nervous system (CNS) and the enteric nervous system (ENS) and sustains metabolic activities. The nerves in the pancreas are categorized as spinal sensory afferent fibers, vagal sensory afferent nerves, autonomic fibers of both sympathetic and parasympathetic divisions, and fibers from the ENS and intrapancreatic ganglia. They innervate different regions and various cell types, which collectively determine physiological functions. Studies have established that the diverse pathological conditions, including pancreatitis, diabetes, and pancreatic tumor, are attributed to aberrant immune reactions; however, it is largely not clear how the neuronal network may influence the disease conditions. Enlightened by the recent advances illuminating the organ-wide neuronal architecture and the dysfunctions in pancreatic disorders, this review will highlight emerging opportunities to explore the cellular interrelationship, particularly the neuroimmune components in pancreatic health and diseases.

Photoredox-Catalyzed Hydroacylation of Azobenzenes with Carboxylic Acids.

Acyl hydrazides are widely found in bioactive compounds and have important applications as versatile synthetic intermediates. In the current report, a photoredox-catalyzed hydroacylation of azobenzenes was disclosed with carboxylic acids as the acylation reagent, affording a variety of N,N'-disubstituted hydrazides. The process possesses the advantages of mild reaction conditions, broad substrate scope, and high efficiency. Preliminary mechanistic investigation indicated that the addition of an acyl radical to the azo compound should be involved.

Nitrogen and phosphorus trends in lake sediments of China may diverge.

The brief history of monitoring nutrient levels in Chinese lake waters limits our understanding of the causes and the long-term trends of their eutrophication and constrains effective lake management. We therefore synthesize nutrient data from lakes in China to reveal the historical changes and project their future trends to 2100 using models. Here we show that the average concentrations of nitrogen and phosphorus in lake sediments have increased by 267% and 202%, respectively since 1850. In the model projections, 2030-2100, the nitrogen concentrations in the studied lakes in China may decrease, for example, by 87% in the southern districts and by 19% in the northern districts. However, the phosphorus concentrations will continue to increase by an average of 25% in the Eastern Plain, Yunnan-Guizhou Plateau, and Xinjiang. Based on this differentiation, we suggest that nitrogen and phosphorus management in Chinese lakes should be carried out at the district level to help develop rational and sustainable environmental management strategies.

Estimating the Heterogeneous Causal Effects of Parent-Child Relationships among Chinese Children with Oppositional Defiant Symptoms: A Machine Learning Approach.

Oppositional defiant symptoms are some of the most common developmental symptoms in children and adolescents with and without oppositional defiant disorder. Research has addressed the close association of the parent-child relationship (PCR) with oppositional defiant symptoms. However, it is necessary to further investigate the underlying mechanism for forming targeted intervention strategies. By using a machine learning-based causal forest (CF) model, we investigated the heterogeneous causal effects of the PCR on oppositional defiant symptoms in children in Chinese elementary schools. Based on the PCR improvement in two consecutive years, 423 children were divided into improved and control groups. The assessment of oppositional defiant symptoms (AODS) in the second year was set as the dependent variable. Additionally, several factors based on the multilevel family model and the baseline AODS in the first year were included as covariates. Consistent with expectations, the CF model showed a significant causal effect between the PCR and oppositional defiant symptoms in the samples. Moreover, the causality exhibited heterogeneity. The causal effect was greater in those children with higher baseline AODS, a worse family atmosphere, and lower emotion regulation abilities in themselves or their parents. Conversely, the parenting style played a positive role in causality. These findings enhance our understanding of how the PCR contributes to the development of oppositional defiant symptoms conditioned by factors from a multilevel family system. The heterogeneous causality in the observation data, established using the machine learning approach, could be helpful in forming personalized family-oriented intervention strategies for children with oppositional defiant symptoms.

Phenotypic and genomic characterization of a multidrug-resistant Salmonella enterica serovar Kentucky ST198 isolated from a patient in China.

OBJECTIVES: The objective of this study was to investigate the resistance mechanisms of a multidrug-resistant Salmonella Kentucky ST198 FJ-2064 isolated from a patient in China. METHODS: The antimicrobial susceptibility of FJ-2064 was determined by the standard disc dilution and broth microdilution methods. The complete genome of FJ-2064 was sequenced using PacBio and Illumina MiSeq platforms. Polymerase chain reaction (PCR) and S1-PFGE were utilized to confirm the mutation sites and the genomic plasmids, respectively. RESULTS: Isolate FJ-2064 belongs to sequence type ST198 and harboured no visible large plasmids, but was concurrent resistant to 22 detected antimicrobial agents including cefotaxime, ciprofloxacin, and azithromycin. The complete genome sequence identified 20 acquired antibiotic resistance genes (ARGs) and five chromosomal mutations in the gyrA and parC genes of the quinolone resistance determining regions (QRDRs) in FJ-2064. In addition, PCR sequencing confirmed that most of the ARGs were clustered on one multidrug-resistant region and a variant of SGI1-K. In particular, the bla-TEM-1 and bla-CTX-M-55, qnrS1, mph(A) genes, which confer resistance to cephalosporins, quinolones, and macrolides respectively, were all located on the multidrug-resistant region. CONCLUSIONS: We have demonstrated one multidrug-resistant region and a variant of SGI1-K in a Salmonella Kentucky ST198 that is co-resistant to cefotaxime, ciprofloxacin, and azithromycin.

Mechanistic and Functional Studies on the Microbial Induction of Wolfiporia cocos Liquid Fermentation Products.

Liquid fermentation is an efficient culture for obtaining polysaccharides from edible mushrooms. In this study, the polysaccharide content and biomass were examined by introducing microorganisms into the Wolfiporia cocos fermentation system. Three edible mushroom co-fermentation systems were established, among which the Wolfiporia cocos-Ganoderma lucidum co-fermentation system significantly increased the mycelial biomass of the system by 57.71% compared to Wolfiporia cocos alone and 91.22% compared to Ganoderma lucidum alone, and the intracellular polysaccharide content was significantly increased. Physiological activities of polysaccharides showed that mycelial polysaccharides in the Wolfiporia cocos-Ganoderma lucidum system had stronger anti-tumor cell value-adding and anti-tumor cell migration activities compared with Wolfiporia cocos and Ganoderma lucidum fermentation alone. The transcriptomic study of Wolfiporia cocos mycelium induced by exogenous substances suggested that the exogenous substances could enhance the intracellular polysaccharide content of Wolfiporia cocos through the upregulation of the expression of α-glycosyltransferase encoded by ALG10 and the downregulation of α-glycosidases encoded by MAN1B in the glycolytic metabolism of Wolfiporia cocos. This study provides a new direction for the transformation of polysaccharides from Wolfiporia cocos and Ganoderma lucidum into functional foods and new product development, and provides an experimental basis.

Metformin suppresses proliferation and glycolysis of gastric cancer by modulating ADAMTS12.

BACKGROUND: Gastric cancer (GC) is a common malignancy with its morbidity increasing worldwide. Hence, it is imperative to develop effective treatments. Studies have shown that metformin has potential antitumor effects. The objective of this study was to probe the antitumor mechanism of metformin in GC. METHODS: The expression of ADAMTS12 in GC tissues and its enrichment pathways were analyzed by bioinformatics methods. ADAMTS12 expression in GC cells was assessed by qRT-PCR. Cell viability and proliferation were analyzed by CCK-8 and colony formation assays, respectively. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of GC cells in different treatment groups were analyzed by Seahorse XP 96, and glycolysis metabolites were detected by corresponding kits. Western blot was employed to analyze the level of glycolysis pathway related protein HK-2, and cell functional assays were conducted to verify the functions of metformin on GC cells. A xenograft model was constructed to validate the inhibitory role of metformin in GC. RESULTS: ADAMTS12 expression was elevated in GC tissues/cells and concentrated in glycolysis pathway. Cell functional assays found that ADAMTS12 promoted the proliferation and glycolysis of GC cells. Rescue experiments showed that metformin could reduce the promoting effect of ADAMTS12 overexpression on the proliferation and glycolysis of GC cells. In vivo studies confirmed that metformin suppressed the proliferation and glycolysis process via ADAMTS12 in GC cells. CONCLUSION: Metformin can repress the proliferation and glycolysis of GC cells via ADAMTS12. The results suggest the potential of ADAMTS12 being a target for the metformin therapy of GC.

GSDMB: A novel, independent prognostic marker and potential new therapeutic target in clear cell renal cell carcinoma.

Gasdermin (GSDM) family members are involved in numerous biological processes, including pyroptosis, as well as in the initiation and progression of various types of cancer. However, the specific role of GSDM genes in clear cell renal cell carcinoma (ccRCC) has yet to be fully clarified. The present study investigated the differential expression and genetic alterations GSDM genes, their effects on prognosis and immune modulation, and their functional enrichment in ccRCC. Several bioinformatics databases were used, including UALCAN, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Metascape, Tumor Immune Estimation Resource, GSCALite and cBioPortal. The results revealed that the expression levels of GSDMA, GSDMB, GSDMC and GSDMD were significantly upregulated in cancer tissues compared with those in paracancerous tissues in patients with ccRCC, whereas the expression of DFNB59 exhibited the opposite trend. The results were experimentally validated in patients with ccRCC, and it was confirmed that the expression levels of GSDMA, GSDMB, GSDMC, GSDMD and GSDME (DFNA5) were significantly enhanced, whereas (PJVK, DFNB59) expression was reduced. In addition, elevated GSDMB, GSDMD and DFNA5 expression levels were clearly associated with worse pathological characteristics of ccRCC, including a high pathological stage and high tumor grade. Furthermore, the high expression levels of GSDMB, GSDMC, GSDMD, DFNA5 and PJVK were shown to be associated with worse overall survival (OS) and progression-free interval in patients with ccRCC. Both univariate and multivariate analyses indicated that the expression of GSDMB was independently associated with the OS of patients with ccRCC. Additionally, a high mutation rate of GSDM genes (33%) was observed in patients with ccRCC, and GSDM gene mutations were also significantly associated with a poor OS in patients with ccRCC. Significant associations between GSDM genes and ccRCC immunoprofiling and drug sensitivity were also determined. In conclusion, the findings of the present study indicated that GSDMB, GSDMD and DFNA5 may be considered promising therapeutic agents and potential biomarkers for patients with ccRCC. Furthermore, GSDMB could act as an independent predictor for the OS of patients with ccRCC.

Long-Term Visual Quality and Pupil Changes after Small-Incision Lenticule Extraction for Eyes without Preoperative Cylinder Refraction.

Purpose: To investigate the long-term changes in visual quality and pupil size after small incision lenticule extraction (SMILE) for eyes without preoperative cylinder refraction. Methods: Thirty-three myopic eyes (33 patients) without preoperative cylinder refraction were corrected using SMILE. Refractive outcomes, corneal curvature, aberrations, contrast sensitivity (CS), and pupil diameter were evaluated preoperatively, and 30 months postoperatively. Results: The 30-month postoperative uncorrected and corrected distance visual acuity (UDVA and CDVA, LogMAR) were -0.10 ± 0.09 and -0.14 ± 0.06, respectively, whereas the preoperative CDVA (LogMAR) was -0.07 ± 0.05. Cylinder refraction of -0.11 ± 0.21 D (ranging from -0.50 to 0.00) was observed at 30 months postoperatively, increasing from the preoperative cylinder refraction of 0.00 ± 0.00 D (P=0.004). Moreover, the centroid coordinates x, y of corneal anterior astigmatic vectors were -0.19 ± 0.22, 0.81 ± 0.33 at 30 months postoperatively, and 0.02 ± 0.28, 0.76 ± 0.51 preoperatively (Px < 0.001 and Py=0.810, respectively). Furthermore, a 15° axis change in the mean anterior corneal astigmatic vector was observed at 30 months postoperatively from the preoperative state, as measured by Pentacam. At 30 months postoperatively, the photopic Log CS reduced significantly with glare at three and six cycles/degrees (P < 0.001 and P=0.015, respectively), a decreased photopic pupil diameter (3.27 ± 0.55 mm vs. 3.10 ± 0.66 mm, P=0.030), and an increased Coma (Z31) and Trefoil (Z3-3) at 4 mm diameter area analysis. However, a significant linear regression relationship was only observed between changes in photopic pupil diameter and changes in photopic Log CS with glare at 12 cycles/degree (P=0.038 and ß = 0.282). Conclusion: Slight cylinder regression was observed with thicker corneal lenticular extraction after SMILE correction of nonastigmatic eyes 30 months postoperatively. This regression was mainly because of the axis changes in anterior corneal astigmatism power. Therefore, a cylinder nomogram modification of 0.25 to 0.50 D is considerable for correcting nonastigmatic myopic eyes with a predicted spherical lenticular thickness over 100 µm.

Sympathetic nerve-enteroendocrine L cell communication modulates GLP-1 release, brain glucose utilization, and cognitive function.

Glucose homeostasis is controlled by brain-gut communications. Yet our understanding of the neuron-gut interface in the glucoregulatory system remains incomplete. Here, we find that sympathetic nerves elevate postprandial blood glucose but restrict brain glucose utilization by repressing the release of glucagon-like peptide-1 (GLP-1) from enteroendocrine L cells. Sympathetic nerves are in close apposition with the L cells. Importantly, sympathetic denervation or intestinal deletion of the adrenergic receptor α2 (Adra2a) augments postprandial GLP-1 secretion, leading to reduced blood glucose levels and increased brain glucose uptake. Conversely, sympathetic activation shows the opposite effects. At the cellular level, adrenergic signaling suppresses calcium flux to limit GLP-1 secretion upon sugar ingestion. Consequently, abrogation of adrenergic signal results in a significant improvement in learning and memory ability. Together, our results reveal a sympathetic nerve-enteroendocrine unit in constraining GLP-1 secretion, thus providing a therapeutic nexus of mobilizing endogenous GLP-1 for glucose management and cognitive improvement.

Transition experiences of patients with post stroke dysphagia and family caregivers: A longitudinal, qualitative study.

BACKGROUND: Stroke patients with dysphagia and family caregivers will experience multiple transitions during the whole process of the disease and various nursing needs will be generated. There is a lack of knowledge about their experiences at different transition stages. Thus, we aimed to explore the transition experiences of patients with post stroke dysphagia and family caregivers from admission to discharge home. METHODS: A semi-structured interview based on Meleis's transition theory was used during hospitalization and telephone follow-up interviews were conducted in the first, third, and sixth month after the diagnosis of dysphagia. Interview transcripts were analyzed using the conventional content analysis method. RESULTS: A total of 17 participants enrolled in the first face-to-face interview, 16 participants took part in the first month's telephone follow-up interview, 14 participants in the third month, and 12 participants in the sixth month. The transition experiences of patients with post stroke dysphagia and family caregivers could be summarized into three themes: (1)transition from onset to admission; (2)transition from discharge to other rehabilitation institutions; and (3)transition from discharge to home. Each theme had identified interrelated subthemes. CONCLUSIONS: The experiences of patients with post stroke dysphagia and family caregivers during transition are a dynamic process with enormous challenges in each phase. Collaboration with health care professionals, follow-up support after discharge, and available community and social support should be integrated into transitional nursing to help patients facilitate their transition.

Never-Ending Learning for Explainable Brain Computing.

Exploring the nature of human intelligence and behavior is a longstanding pursuit in cognitive neuroscience, driven by the accumulation of knowledge, information, and data across various studies. However, achieving a unified and transparent interpretation of findings presents formidable challenges. In response, an explainable brain computing framework is proposed that employs the never-ending learning paradigm, integrating evidence combination and fusion computing within a Knowledge-Information-Data (KID) architecture. The framework supports continuous brain cognition investigation, utilizing joint knowledge-driven forward inference and data-driven reverse inference, bolstered by the pre-trained language modeling techniques and the human-in-the-loop mechanisms. In particular, it incorporates internal evidence learning through multi-task functional neuroimaging analyses and external evidence learning via topic modeling of published neuroimaging studies, all of which involve human interactions at different stages. Based on two case studies, the intricate uncertainty surrounding brain localization in human reasoning is revealed. The present study also highlights the potential of systematization to advance explainable brain computing, offering a finer-grained understanding of brain activity patterns related to human intelligence.

Ligand-Controlled Cobalt-Catalyzed Regiodivergent and Stereoselective Ring-Opening Isomerization of Vinyl Cyclopropanes.

A ligand-controlled regiodivergent and stereoselective ring-opening isomerization of vinylcyclopropane was developed with cobalt catalysis. Employing the commercially available Xantphos ligand, the reactions afforded exclusively linear-type 1,3-dienes as the products. Interestingly, when switching the ligand to an amido-diphosphine ligand (PNP), branched-type 1,3-dienes were obtained with high regioselectivity and stereoselectivity. Preliminary mechanistic investigations suggested that a π-allyl metal and a metal-hydride species are involved as key intermediates in the two transformations, respectively.

Climate change drove the route shift of the ancient Silk Road in two distinct ways.

Although climate change has convincingly been linked to the evolution of human civilization on different temporal scales, its role in influencing the spatial patterns of ancient civilizations has rarely been investigated. The northward shift of the ancient Silk Road (SR) route from the Tarim Basin (TB) to the Junggar Basin during ∼420-850 CE provides the opportunity to investigate the relationship between climate change and the spatial evolution of human societies. Here, we use a new high-resolution chironomid-based temperature reconstruction from arid China, combined with hydroclimatic and historical datasets, to assess the possible effects of climate fluctuations on the shift of the ancient SR route. We found that a cooling/drying climate in the TB triggered the SR route shift during ∼420-600 CE. However, a warming/wetting climate during ∼600-850 CE did not inhibit this shift, but instead promoted it, because of the favorable climate-induced geopolitical conflicts between the Tubo Kingdom and the Tang Dynasty in the TB. Our findings reveal two distinct ways in which climate change drove the spatial evolution of human civilization, and they demonstrate the flexibility of societal responses to climate change.

Combined analysis of Polygonum cuspidatum transcriptome and metabolome revealed that PcMYB62, a transcription factor, responds to methyl jasmonate and inhibits resveratrol biosynthesis.

A comparative transcriptomic and metabolomic analysis of Polygonum cuspidatum leaves treated with MeJA was carried out to investigate the regulatory mechanisms of its active compounds. A total of 692 metabolites and 77,198 unigenes were obtained, including 200 differentially accumulated metabolites and 6819 differentially expressed genes. We screened potential regulatory transcription factors involved in resveratrol and flavonoids biosynthesis, and successfully identified an MYB transcription factor, PcMYB62, which could significantly decrease the resveratrol content in P. cuspidatum leaves when over-expressed. PcMYB62 could directly bind to the MBS motifs in the promoter region of stilbene synthase (PcSTS) gene and repress its expression. Besides, PcMYB62 could also repress PcSTS expression and resveratrol biosynthesis in transgenic Arabidopsis thaliana. Our results provide abundant candidate genes for further investigation, and the new finding of the inhibitory role of PcMYB62 on the resveratrol biosynthesis could also potentially be used in metabolic engineering of resveratrol in P. cuspidatum.