Cytochrome P450 SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11.

Accumulating salinity in soil critically affected growth, development, and yield in plant. However, the mechanisms of plant against salt stress largely remain unknown. Herein, we identified a gene named SmCYP78A7a, which encoded a cytochrome P450 monooxygenase and belonged to the CYP78A sub-family, and its transcript level was significantly up-regulated by salt stress and down-regulated by dehydration stress. SmCYP78A7a located in the endoplasmic reticulum. Silencing of SmCYP78A7a enhanced susceptibility of eggplant to salt stress, and significantly down-regulated the transcript levels of salt stress defense related genes SmGSTU10 and SmWRKY11 as well as increased hydrogen peroxide (H2O2) content and decreased catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) enzyme activities. In addition, SmCYP78A7a transient expression enhanced eggplant tolerance to salt stress. By chromatin immunoprecipitation PCR (ChIP-PCR), luciferase reporter assay, and electrophoretic mobility shift assay (EMSA), SmWRKY11 activated SmCYP78A7a expression by directly binding to the W-box 6-8 (W-box 6, W-box 7, and W-box 8) within SmCYP78A7a promoter to confer eggplant tolerance to salt stress. In summary, our finds reveal that SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11, and provide a new insight into regulatory mechanisms of eggplant to salt stress.

Dysregulation of phosphoenolpyruvate carboxykinase in cancers: A comprehensive analysis.

BACKGROUND: Phosphoenolpyruvate carboxykinase (PEPCK) plays a crucial role in gluconeogenesis, glycolysis, and the tricarboxylic acid cycle by converting oxaloacetate into phosphoenolpyruvate. Two distinct isoforms of PEPCK, specifically cytosolic PCK1 and mitochondrial PCK2, have been identified. Nevertheless, the comprehensive understanding of their dysregulation in pan-cancer and their potential mechanism contributing to signaling transduction pathways remains elusive. METHODS: We conducted comprehensive analyses of PEPCK gene expression across 33 diverse cancer types using data from The Cancer Genome Atlas (TCGA). Multiple public databases such as HPA, TIMER 2.0, GEPIA2, cBioPortal, UALCAN, CancerSEA, and String were used to investigate protein levels, prognostic significance, clinical associations, genetic mutations, immune cell infiltration, single-cell sequencing, and functional enrichment analysis in patients with pan-cancer. PEPCK expression was analyzed about different clinical and genetic factors of patients using data from TCGA, GEO, and CGGA databases. Furthermore, the role of PCK2 in Glioma was examined using both in vitro and in vivo experiments. RESULTS: The analysis we conducted revealed that the expression of PEPCK is involved in both clinical outcomes and immune cell infiltration. Initially, we verified the high expression of PCK2 in GBM cells and its role in metabolic reprogramming and proliferation in GBM. CONCLUSION: Our study showed a correlation between PEPCK (PCK1 and PCK2) expression with clinical prognosis, gene mutation, and immune infiltrates. These findings identified two possible predictive biomarkers across different cancer types, as well as a comprehensive analysis of PCK2 expression in various tumors, with a focus on GBM.

Gasdermin D drives focal Crystalline Thrombotic Microangiopathy by accelerating Immunothrombosis and Necroinflammation.

Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure, but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein serving as the final downstream effector of pyroptosis/interleukin (IL)-1pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd-deficiency ameliorated immunothrombosis, acute tissue injury and failure. Gsdmd-/- mice exhibited a decrease in mature IL-1, as well as in neutrophil maturation, 2 integrin activation, and recruitment to TMA lesions, where they formed reduced neutrophil extracellular traps both in arteries and interstitial tissue. The GSDMD inhibitor disulfiram dose-dependently suppressed human neutrophil pyroptosis in response to cholesterol crystals. Experiments with GSDMD-deficient human induced pluripotent stem cell-derived neutrophils confirmed the involvement of GSDMD in neutrophil 2 integrin activation, maturation as well as pyroptosis. Both prophylactic and therapeutic administration of disulfiram protected mice from focal TMA, acute tissue injury and failure. Our data identify GSDMD as a key mediator of focal crystalline TMA and its consequences: ischemic tissue infarction and organ failure. GSDMD could potentially serve as a therapeutic target for systemic forms of TMA.

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up.

OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

Intelligent Identification of Cerebrospinal Fluid for the Diagnosis of Parkinson's Disease.

Cerebrospinal fluid (CSF) biomarkers are more sensitive than the Movement Disorder Society (MDS) criteria for detecting prodromal Parkinson's disease (PD). Early detection of PD provides the best chance for successful implementation of disease-modifying treatments, making it crucial to effectively identify CSF extracted from PD patients or normal individuals. In this study, an intelligent sensor array was built by using three metal-organic frameworks (MOFs) that exhibited varying catalytic kinetics after reacting with potential protein markers. Machine learning algorithms were used to process fingerprint response patterns, allowing for qualitative and quantitative assessment of the proteins. The results were robust and capable of discriminating between PD and non-PD patients via CSF detection. The k-nearest neighbor regression algorithm was used to predict MDS scores with a minimum mean square error of 38.88. The intelligent MOF sensor array is expected to promote the detection of CSF biomarkers due to its ability to identify multiple targets and could be used in conjunction with MDS criteria and other techniques to diagnose PD more sensitively and selectively.

RDH12-associated retinal degeneration caused by a homozygous pathogenic variant of 146C>T and literature review.

AIM: To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant. RESULTS: A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied. CONCLUSION: An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

Microglia in Microbiota-Gut-Brain Axis: A Hub in Epilepsy.

There is growing concern about the role of the microbiota-gut-brain axis in neurological illnesses, and it makes sense to consider microglia as a critical component of this axis in the context of epilepsy. Microglia, which reside in the central nervous system, are dynamic guardians that monitor brain homeostasis. Microglia receive information from the gut microbiota and function as hubs that may be involved in triggering epileptic seizures. Vagus nerve bridges the communication in the axis. Essential axis signaling molecules, such as gamma-aminobutyric acid, 5-hydroxytryptamin, and short-chain fatty acids, are currently under investigation for their participation in drug-resistant epilepsy (DRE). In this review, we explain how vagus nerve connects the gut microbiota to microglia in the brain and discuss the emerging concepts derived from this interaction. Understanding microbiota-gut-brain axis in epilepsy brings hope for DRE therapies. Future treatments can focus on the modulatory effect of the axis and target microglia in solving DRE.

Sahara's surface transformation forced an abrupt hydroclimate decline and Neolithic culture transition in northern China.

The remote forcing from land surface changes in the Sahara is hypothesized to play a pivotal role in modulating the intensity of the East Asian summer monsoon (EASM) through ocean-atmospheric teleconnections. This modulation has far-reaching consequences, particularly in facilitating societal shifts documented in northern China. Here, we present a well-dated lake-level record from the Daihai Lake Basin in northern China, providing quantitative assessments of Holocene monsoonal precipitation and the consequent migrations of the northern boundary of the EASM. Our reconstruction, informed by a water-and-energy balance model, indicates that annual precipitation reached ∼700 mm during 8-5 ka, followed by a rapid decline to ∼550 mm between 5 and 4 ka. This shift coherently aligns with a significant ∼300 km northwestward movement of the EASM northern boundary during the Middle Holocene (MH), in contrast to its current position. Our findings underscore that these changes cannot be entirely attributed to orbital forcing, as corroborated by simulation tests. Climate model simulations deployed in our study suggest that the presence of the Green Sahara during the MH significantly strengthened the EASM and led to a northward shift of the monsoon rainfall belt. Conversely, the Sahara's reversion to a desert landscape in the late Holocene was accompanied by a corresponding southward retraction of monsoon influence. These dramatic hydroclimate changes during ∼5-4 ka likely triggered or at least contributed to a shift in Neolithic cultures and societal transformation in northern China. With decreasing agricultural productivity, communities transitioned from millet farming to a mixed rainfed agriculture and animal husbandry system. Thus, our findings elucidate not only the variability of the EASM but also the profound implications of a remote forcing, such as surface transformations of the Sahara, on climatic changes and cultural evolution in northern China.

Phosphor-free micro-pyramid InGaN-based white light-emitting diode with a high color rendering index on a ß-Ga2O3 substrate.

We demonstrate the InGaN/GaN-based monolithic micro-pyramid white (MPW) vertical LED (VLED) grown on (-201)-oriented ß-Ga2O3 substrate by selective area growth. The transmission electron microscopy (TEM) reveals an almost defect-free GaN pyramid structure on (10-11) sidewalls, including stacked dual-wavelength multi-quantum wells (MQWs). From the electroluminescence (EL) spectra of the fabricated MPW VLED, a white light emission with a high color rendering index (CRI) of 97.4 is achieved. Furthermore, the simulation shows that the light extraction efficiency (LEE) of the MPW VLED is at least 4 times higher compared with the conventional planar LED. These results show that the MPW VLED grown on ß-Ga2O3 has great potential for highly efficient phosphor-free white light emission.

Transcriptome analysis of the hepatopancreas from the Litopenaeus vannamei infected with different flagellum types of Vibrio alginolyticus strains.

Vibrio alginolyticus, one of the prevalently harmful Vibrio species found in the ocean, causes significant economic damage in the shrimp farming industry. Its flagellum serves as a crucial virulence factor in the invasion of host organisms. However, the processes of bacteria flagella recognition and activation of the downstream immune system in shrimp remain unclear. To enhance comprehension of this, a ΔflhG strain was created by in-frame deletion of the flhG gene in V. alginolyticus strain HN08155. Then we utilized the transcriptome analysis to examine the different immune responses in Litopenaeus vannamei hepatopancreas after being infected with the wild type and the mutant strains. The results showed that the ΔflhG strain, unlike the wild type, lost its ability to regulate flagella numbers negatively and displayed multiple flagella. When infected with the hyperflagella-type strain, the RNA-seq revealed the upregulation of several immune-related genes in the shrimp hepatopancreas. Notably, two C-type lectins (CTLs), namely galactose-specific lectin nattectin and macrophage mannose receptor 1, and the TNF receptor-associated factor (TRAF) 6 gene were upregulated significantly. These findings suggested that C-type lectins were potentially involved in flagella recognition in shrimp and the immune system was activated through the TRAF6 pathway after flagella detection by CTLs.

Enhancing Performance of GaN/Ga2 O3 P-N Junction Uvc Photodetectors via Interdigitated Structure.

Ga2 O3 -based Ultraviolet-C photodetector (UVCPD) is considered the most promising UVCPD at present and is divided into Metal-Semiconductor-Metal (MSM) and PN junction types. Compared with MSM-PDs, PN-PDs exhibit superior transient performance due to the built-in electric field. However, current Ga2 O3 -based PN-PDs lack consideration for carrier collection and electric field distribution. In this study, PN-PDs with an interdigital n-Ga2 O3 layer and finger electrodes are fabricated on p-GaN/n-Ga2 O3 epilayers. Ultrafast response times of 31 µs (1/e decay) and 2.76 µs (fast component) are realized, which outperforms all Ga2 O3 UVC-PDs up to now. Under 0 V self-powered, the responsivity (0.25 A W-1 ) of interdigital PD is enhanced by the interdigital electrode structure due to increasing carriers' collection length. Under bias, the performances of interdigital PD with 41.7 A W-1 responsivity and 8243 selection ratios are significantly elevated by enhancing the built-in electric field in the Ga2 O3 region, which is 34.76 and 39.4 times those of traditional PDs, respectively. The intrinsic enhancing mechanism of interdigital structure is also investigated by interdigital PDs with various electrode spacings and perimeters. In summary, this paper not only reports a highly performed interdigitated structure p-GaN/n-Ga2 O3 UVCPDs, but also provides guidelines for structure design in Ga2 O3 -based PN-PDs.

A low androgen state impairs erectile function by suppressing EPAC1 in rat penile corpus cavernosum.

Background: Exchange proteins activated by cAMP 1 (EPAC1) can promote vasodilatation by regulating endothelial nitric oxide synthase (eNOS) activity through the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway and prevent vascular smooth muscle contraction by restraining the ras homolog gene family, member A/Rho-associated coiled-coil forming protein kinase (RhoA/ROCK) pathway. However, the relationship among EPAC1, androgen and erectile function is still unknown. Therefore, we attempted to investigate whether EPAC1 expresses in penile corpus cavernosum of rats and how EPAC1 affects erectile function under low androgenic conditions. Methods: Thirty 8-week-old Sprague-Dawley male rats were randomly divided into six groups (n=5): sham operation (sham), castrated, castrated + testosterone replacement (castrated + T), sham + EPAC1 over-expression lentivirus (sham + EPAC1), castrated + empty lentivirus vector (castrated + empty vector), and castrated + EPAC1. Four weeks after the operation, the lentivirus vectors carrying the EPAC1 gene were injected into the penile corpus cavernosum of the sham + EPAC1 and castrated + EPAC1 groups (1×108 TU/mL, 20 µL per rat). A week after injection, the ratio of maximum intracavernous pressure to mean arterial pressure (ICPmax/MAP) and the levels of serum testosterone (T), nitric oxide (NO), the active form of RhoA (RhoA-GTP), AKT, phospho-AKT (p-AKT), eNOS, phospho-eNOS (p-eNOS), p-AKT/AKT, p-eNOS/eNOS and EPAC1 levels were measured. Results: In comparison to the sham group, ICPmax/MAP and EPAC1 content in the castrated group were significantly reduced. EPAC1 is primarily located in the cyto-membrane and cytoplasm of endothelial cells and smooth muscle cells in the rat penile corpus cavernosum. In comparison to the sham group, the T, ICPmax/MAP and NO levels of the castrated group were significantly reduced (P<0.01). Meanwhile, the RhoA-GTP concentration in the castrated + EPAC1 group was reduced in comparison with the castrated + empty vector group (P<0.01). Compared with the castrated + empty vector group, the p-AKT/AKT, EPAC1 and p-eNOS/eNOS levels in the castrated + EPAC1 group were significantly increased (P<0.05). Conclusions: Androgen deficiency can suppress EPAC1 expression in the penile corpus cavernosum of rats, while the up-regulation of which can improve the erectile function of castrated rats.

Macrophages and fibrosis: how resident and infiltrating mononuclear phagocytes account for organ injury, regeneration or atrophy.

Mononuclear phagocytes (MP), i.e., monocytes, macrophages, and dendritic cells (DCs), are essential for immune homeostasis via their capacities to clear pathogens, pathogen components, and non-infectious particles. However, tissue injury-related changes in local microenvironments activate resident and infiltrating MP towards pro-inflammatory phenotypes that contribute to inflammation by secreting additional inflammatory mediators. Efficient control of injurious factors leads to a switch of MP phenotype, which changes the microenvironment towards the resolution of inflammation. In the same way, MP endorses adaptive structural responses leading to either compensatory hypertrophy of surviving cells, tissue regeneration from local tissue progenitor cells, or tissue fibrosis and atrophy. Under certain circumstances, MP contribute to the reversal of tissue fibrosis by clearance of the extracellular matrix. Here we give an update on the tissue microenvironment-related factors that, upon tissue injury, instruct resident and infiltrating MP how to support host defense and recover tissue function and integrity. We propose that MP are not intrinsically active drivers of organ injury and dysfunction but dynamic amplifiers (and biomarkers) of specific tissue microenvironments that vary across spatial and temporal contexts. Therefore, MP receptors are frequently redundant and suboptimal targets for specific therapeutic interventions compared to molecular targets upstream in adaptive humoral or cellular stress response pathways that influence tissue milieus at a contextual level.

Bioinformatic and functional characterization of cyclic-di-GMP metabolic proteins in Vibrio alginolyticus unveils key diguanylate cyclases controlling multiple biofilm-associated phenotypes.

The biofilm lifestyle is critical for bacterial survival and proliferation in the fluctuating marine environment. Cyclic diguanylate (c-di-GMP) is a key second messenger during bacterial adaptation to various environmental signals, which has been identified as a master regulator of biofilm formation. However, little is known about whether and how c-di-GMP signaling regulates biofilm formation in Vibrio alginolyticus, a globally dominant marine pathogen. Here, a large set of 63 proteins were predicted to participate in c-di-GMP metabolism (biosynthesis or degradation) in a pathogenic V. alginolyticus strain HN08155. Guided by protein homology, conserved domains and gene context information, a representative subset of 22 c-di-GMP metabolic proteins were selected to determine which ones affect biofilm-associated phenotypes. By comparing phenotypic differences between the wild-type and mutants or overexpression strains, we found that 22 c-di-GMP metabolic proteins can separately regulate different phenotypic outputs in V. alginolyticus. The results indicated that overexpression of four c-di-GMP metabolic proteins, including VA0356, VA1591 (CdgM), VA4033 (DgcB) and VA0088, strongly enhanced rugose colony morphotypes and strengthened Congo Red (CR) binding capacity, both of which are indicators of biofilm matrix overproduction. Furthermore, rugose enhanced colonies were accompanied by increased transcript levels of extracellular polysaccharide (EPS) biosynthesis genes and decreased expression of flagellar synthesis genes compared to smooth colonies (WTpBAD control), as demonstrated by overexpression strains WTp4033 and ∆VA4033p4033. Overall, the high abundance of c-di-GMP metabolic proteins in V. alginolyticus suggests that c-di-GMP signaling and regulatory system could play a key role in its response and adaptation to the ever-changing marine environment. This work provides a robust foundation for the study of the molecular mechanisms of c-di-GMP in the biofilm formation of V. alginolyticus.

Current spreading structure of GaN-based vertical-cavity surface-emitting lasers.

Indium tin oxide (ITO) is often used as a current spreading layer in the GaN-based vertical-cavity surface-emitting lasers (VCSELs). However, the absorption coefficient of ITO is significant, which reduces the laser output power, raises the threshold, and makes VCSELs hardly lase in the ultraviolet range. To find a transparent conductive structure that can replace ITO, we propose a periodic p-AlGaN/u-GaN/p-GaN structure. In the simulation of light-emitting diodes, the optimized parameter is obtained with multi-period 10 nm p-Al0.1Ga0.9N/2 nm u-GaN/8 nm p-GaN combined with n-GaN/n-Al0.2Ga0.8N in the n region. Applying the structure to 435 nm VCSELs and comparing it to a common VCSEL with the ITO current spreading layer, it can be found that the new structure reduces the threshold from 9.17 to 3.06 kA/cm2. The laser power increases from 1.33 to 15.4 mW. The optimized structure has a high laser power and a lower threshold, which can be used in future investigations.

TRIM6: An Upregulated Biomarker with Prognostic Significance and Immune Correlations in Gliomas.

This study investigates the expression and prognostic value of TRIM6 in gliomas, the most prevalent primary brain and spinal cord tumors. Our results show that TRIM6 is predominantly overexpressed in glioma tissues and is associated with reduced overall survival, disease-specific survival, and progression-free interval. Furthermore, TRIM6 expression is correlated with WHO grade and primary treatment outcomes. Functional analysis indicates that interactions between cytokines and their receptors play a critical role in the prognosis of glioma patients. A protein-protein interaction network reveals 10 hub genes closely linked to cytokine-cytokine receptor interaction. In vitro experiments demonstrate that silencing TRIM6 impairs the proliferation, invasion, and migration of glioma cells, while overexpressing TRIM6 enhances these abilities. Additionally, TRIM6 expression is positively associated with the abundance of innate immune cells and negatively associated with the abundance of adaptive immune cells. In summary, TRIM6 is significantly upregulated in gliomas and linked to poor prognosis, making it a potential diagnostic and prognostic biomarker. TRIM6 plays a crucial role in promoting cell viability, clonogenic potential, migration, and invasion in glioma cells. It may regulate glioma progression by modulating cytokine-cytokine receptor interaction, leading to an inflammatory response and an imbalance in immunomodulation, thereby representing a potential therapeutic target.

Electrochemical Late-Stage Functionalization.

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical or biological activities. LSF can thus greatly accelerate the development of medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical molecular synthesis has emerged as an environmentally friendly platform for the transformation of organic compounds. Over the past decade, electrochemical late-stage functionalization (eLSF) has gained major momentum, which is summarized herein up to February 2023.

Overwintering performance of bamboo leaves, and establishment of mathematical model for the distribution and introduction prediction of bamboos.

Bamboo has great economic values and is used extensively in many industries, and their natural distribution range was divided into 12 zones in China according to the temperature of their geographical distribution in previous works. Different bamboo species had significantly different abilities in low-temperature tolerance, which need to be considered carefully during ex-situ introduction. In this paper, we observed and evaluated the low-temperature damage of 19 bamboo species in winter, and measured the physiological changes of bamboo leaves. A total of 3060 leaf samples were obtained from 102 core collections in 34 bamboo species from the 5 regions of Chinese mainland for anatomical comparison, in order to screen out the key anatomical indicators related to their low-temperature tolerance and to establish a mathematical prediction model for bamboo introduction. The results showed that the low-temperature resistance of clustered bamboos was generally lower than that of the scattered bamboos. The decreased temperature led to the constant decrease of net photosynthetic rate and transpiration rate, but the increase of soluble sugar content in all bamboo species. There was no dormancy for all bamboo species in winter. The temperate bamboos showed lower photosynthesis as compared to tropical bamboos in winter. The leaf shape of bamboos was closely related to their distribution. A total of 13 leaf indicators were screened and more suitable to estimate the low-temperature tolerant abilities of bamboos and to predict their distribution. The MNLR (multiple nonlinear regression) mathematical model showed the highest fitting degree and the optimal prediction ability in the potential northernmost introduction range of bamboos. This study lay a foundation for bamboo introduction, and could also reduce the economic losses caused by the wrong introduction.

The Effects of Drug Exposure and Single Nucleotide Polymorphisms on Aaptinib-Induced Severe Toxicities in Solid Tumors.

To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities. METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250 mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed. RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA, and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P < 0.01; M1-1, P < 0.01) and high-grade antiangiogenetic toxicities (APA, P = 0.034; P < 0.05), including hypertension, proteinuria, and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P < 0.001) and M1-1 (P < 0.01), whereas CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P < 0.01). CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need consideration in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. SIGNIFICANCE STATEMENT: Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

Continuous Flow Electrochemistry Enables Practical and Site-Selective C-H Oxidation.

The selective oxygenation of ubiquitous C(sp3 )-H bonds remains a highly sought-after method in both academia and the chemical industry for constructing functionalized organic molecules. However, it is extremely challenging to selectively oxidize a certain C(sp3 )-H bond to afford alcohols due to the presence of multiple C(sp3 )-H bonds with similar strength and steric environment in organic molecules, and the alcohol products being prone to further oxidation. Herein, we present a practical and cost-efficient electrochemical method for the highly selective monooxygenation of benzylic C(sp3 )-H bonds using continuous flow reactors. The electrochemical reactions produce trifluoroacetate esters that are resistant to further oxidation but undergo facile hydrolysis during aqueous workup to form benzylic alcohols. The method exhibits a broad scope and exceptional site selectivity and requires no catalysts or chemical oxidants. Furthermore, the electrochemical method demonstrates excellent scalability by producing 115 g of one of the alcohol products. The high site selectivity of the electrochemical method originates from its unique mechanism to cleave benzylic C(sp3 )-H bonds through sequential electron/proton transfer, rather than the commonly employed hydrogen atom transfer (HAT).