Establishing a Ten Disulfidptosis-related Gene Signature for Prognostic Prediction in Skin Cutaneous Melanoma.

AIM: Disulfidptosis is a new metabolic-related regulated cell death associated with cancer growth. This study aimed to investigate the molecular mechanisms associated with disulfidptosis in skin cutaneous melanoma (SKCM) and establish a disulfidptosis-related gene signature for prognostic prediction in SKCM. METHODS: Disulfidptosis-associated genes were identified from RNA-seq data of SKCM. A risk score signature was developed and validated through univariate Cox and LASSO analyses. Additionally, the immune microenvironment related to the risk score signature was investigated. Finally, a disulfidptosis-related genes-transcription factor -miRNA network was developed, and the expression levels of five disulfidptosis-related genes were initially verified in SKCM cell lines. RESULTS: A total of 107 disulfidptosis-related differentially expressed genes in SKCM samples were identified. A ten-disulfidptosis-gene signature was established, including BIN2, CCL3L3, CCL8, CD79A, CIITA, CXCR3, DEFB1, GPR171, IL2RB, and SOCS1. The SKCM samples were divided into high- and low-risk groups, of which samples in the low-risk group showed better survival performance. The receiver operating characteristic curve analysis confirmed the good potency of the disulfidptosis-related gene prognostic model. Except for DEFB1, the other nine genes were positively related with T cell CD8+, T cell CD4+ memory activated, T cell gamma delta, NK cell activated, and macrophage M1, and they were all negatively related with NK cell resting, macrophage M0, macrophage M2, and mast cell activated. Finally, we verified downregulated levels of SOCS1 and DEFB1 and upregulated CXCR3, BIN2, and CCL3L3 in A875 and A375. CONCLUSION: We successfully established ten disulfidptosis-related genes' prediction prognostic signatures for SKCM patients.

Identification of distinct symptom profiles in prostate cancer patients with cancer-related cognitive impairment undergoing androgen deprivation therapy: A latent class analysis.

Objective: To identify latent classes of cognitive impairment and co-occurring symptoms (fatigue, pain, sleep disturbance, depression) as clusters in patients with prostate cancer undergoing androgen deprivation therapy and to explore the predictors among distinct latent classes. Methods: A total of 228 patients with prostate cancer were recruited in this cross-sectional study. The assessment instrument included the Perceived Cognitive Impairment Scale, the Fatigue Severity Scale, the Athens Insomnia Scale, the Brief Pain Inventory, the Patient Health Questionnaire-9, the UCLA Loneliness Scale, the International Physical Activity Questionnaire - Short Form, the Charlson comorbidity index, and General Information questionnaire. The identification of different patient subgroups was done by the latent class analysis. Results: The study identified three distinct latent classes: all low symptoms (class 1, 32%), high depression symptoms (class 2, 37.7%), and high physical symptoms (fatigue, sleep disturbance, and pain) with high cognitive impairment (class 3, 30.3%). Patients who had higher Charlson comorbidity index (P = 0.003) scores were more likely to be classified in class 3. Patients with higher loneliness scores (P < 0.001; P < 0.001) were significantly more likely to fall into class two or three than in class 1. However, having a higher level of physical activity (P = 0.014; P < 0.001) increased the likelihood of being in class 1. Conclusions: This study exhibited the inter-individual variability of symptom experience in prostate cancer patients with cognitive impairment undergoing androgen deprivation therapy. The result suggests that more emphasis should be placed on screening for fatigue, sleep disturbance, and pain, and future interventions should focus on loneliness and physical activity.

Analysis of the pharmacokinetics and efficacy of RBD1016 - A GalNAc-siRNA targeting Hepatitis B Virus X gene using semi-mechanistic PK/PD model.

Small interference RNA (siRNA) is a class of short double-stranded RNA molecules that cause mRNA degradation through an RNA interference mechanism and is a promising therapeutic modality. RBD1016 is a siRNA drug in clinical development for the treatment of chronic Hepatitis B Virus (HBV) infection, which contains a conjugated with N-acetylglucosamine moiety that can facilitate its hepatic delivery. We aimed to construct a semi-mechanistic model of RBD1016 in pre-clinical animals, to elucidate the pharmacokinetic/pharmacodynamic (PK/PD) profiles in mice and PK profiles in monkeys, which can lay the foundation for potential future translation of RBD1016 PK and PD from the pre-clinical stage to the clinic stage. The proposed semi-mechanistic PK/PD model fitted PK and PD data in HBV transgenic mice well and described plasma and liver concentrations in the monkeys well. The simulation results showed that our model has a reasonable predictive ability for Hepatitis B surface antigen (HBsAg) levels after multiple dosing in mice. Further PK and PD data for RBD1016, including clinical data, will assist in refining the model presented here. Our current effort focused on model building for RBD1016, we anticipate that the model could apply to other GalNAc-siRNA drugs.

Preparation of Autoclavable and Injectable Silk Fibroin Cryogels for Tissue Engineering Applications.

A cryogel is a supermacroporous gel network that is generated at subzero temperatures by polymerizing monomers or gelating polymeric precursors. Since cryogels possess inherent characteristics such as interconnected macroporous structures, excellent mechanical properties, and high resistance to autoclave sterilization, they are highly desirable for tissue engineering and regenerative medicine. Silk fibroin, a natural protein obtained from Bombyx mori silkworms, is an excellent raw material for cryogel preparation. The aim of this study was to establish a controlled method for preparing silk fibroin cryogels with suitable properties for application as tissue engineering scaffolds. Using a dual crosslinking strategy consisting of low-temperature radical polymerization coupled with methanol-induced conformational transformation, porous cryogels were prepared. The cryogels displayed many unique characteristics, such as an interconnected macroporous structure, a high water absorption capacity, water-triggered shape memory, syringe injectability and strong resilience to autoclave sterilization. Furthermore, the cryogels demonstrated excellent biocompatibility and cell affinity, facilitating cell adhesion, migration, and proliferation. The interconnected supermacroporous architecture resembling the native extracellular matrix, together with their unique physical properties and autoclaving stability, suggested that cryogels are promising candidate scaffolds for tissue engineering and cell therapy. This article is protected by copyright. All rights reserved.

Radioactive hybrid semiconducting polymer nanoparticles for imaging-guided tri-modal therapy of breast cancer.

Due to the rapid progression and aggressive metastasis of breast cancer, its diagnosis and treatment remain a great challenge. The simultaneous inhibition of tumor growth and metastasis is necessary for breast cancer to obtain ideal therapeutic outcomes. We herein report the development of radioactive hybrid semiconducting polymer nanoparticles (SPNH) for imaging-guided tri-modal therapy of breast cancer. Two semiconducting polymers are used to form SPNH with a diameter of around 60 nm via nano-coprecipitation and they are also labeled with iodine-131 (131I) to enhance the imaging functions. The formed SPNH show good radiolabeling stability and excellent photodynamic and photothermal effects under 808 nm laser irradiation to produce singlet oxygen (1O2) and heat. Moreover, SPNH can generate 1O2 with ultrasound irradiation via their sonodynamic properties. After intravenous tail vein injection, SPNH can effectively accumulate in the subcutaneous 4T1 tumors of living mice as verified via fluorescence and single photon emission computed tomography (SPECT) imaging. With the irradiation of tumors using an 808 nm laser and US, SPNH mediate photodynamic therapy (PDT), photothermal therapy (PTT) and sonodynamic therapy (SDT) to kill tumor cells. Such a tri-modal therapy leads to an improved efficacy in inhibiting tumor growth and suppressing tumor metastasis compared to the sole SDT and combinational PDT-PTT. This study thus demonstrates the applications of SPNH to diagnose tumors and combine different therapies for effective breast cancer treatment.

Endoscopic Bilateral Nipple-sparing Mastectomy via a Single Axillary Incision with Immediate Pre-pectoral Implant-based Breast Reconstruction.

Oncoplastic breast surgery, with its focus on improving cosmetic outcomes while maintaining oncological safety, has fundamentally transformed the landscape of breast cancer surgical treatment, giving rise to an array of techniques for breast reconstruction. Nipple-sparing mastectomy (NSM) with immediate implant-based breast reconstruction (IBBR) has emerged as a cornerstone in managing early breast cancer. Aligned with the principles of minimally invasive surgery, recent years have witnessed the widespread integration of endoscopic approaches in breast surgery, encompassing procedures like endoscopic breast-conserving surgery (E-BCS) and endoscopic nipple-sparing mastectomy (E-NSM), among others. Capitalizing on the advantages of inconspicuous and shorter incisions, improved visibility, and the avoidance of radiation therapy, the popularity of E-NSM with IBBR is on the rise. However, conventional E-NSM with IBBR often requires two or more incisions, which can result in suboptimal cosmetic outcomes and even prosthesis loss.This paper presents a comprehensive account of the intricate surgical procedures involved in endoscopic bilateral nipple-sparing mastectomy with immediate pre-pectoral implant-based breast reconstruction. The insights shared are drawn from the collective experience of our institution. Notable benefits associated with the described surgical approach encompass enhanced cosmetic outcomes, improved postoperative quality of life, and enhanced physiological functions attributable to the application of pre-pectoral implant-based breast reconstruction through a single incision.

Chemical Bath Deposition of SnO2 Films on PEN/ITO Substrates for Efficient Flexible Perovskite Solar Cells.

Flexible perovskite solar cells (f-PSCs) have achieved significant success. However, high-quality tin dioxide (SnO2) electron transport layers (ETLs) fabricated via chemical bath deposition (CBD) have not been achieved on flexible PEN/ITO substrates. This limitation is primarily due to the corrosion of the poor-quality ITO layer by the strongly acidic CBD solution. Here, we analyzed the reasons for the poor corrosion resistance of ITO films on PEN substrate from multiple perspectives, such as element composition, microstructure, and crystallinity. Then, we proposed a modified CBD method for SnO2 films suitable for flexible PEN/ITO substrates. We employed SnCl2·2H2O as the tin source and regulated the pH of the CBD solution by NH3·H2O, which effectively avoided the corrosion of the ITO layer by the CBD solution and achieved high-quality SnO2 films on the ITO layers. Compared to the commercial SnO2 dispersion, the SnO2 films prepared by this method have smaller grains and higher transmittance. As a result, we achieved an unprecedented power conversion efficiency (PCE) of 20.71% for f-PSCs fabricated on PEN/ITO substrates with SnO2 ETLs by CBD method. This breakthrough facilitates the development of high-performance f-PSCs by a low-cost and large-scale chemical bath deposition of high-quality ETLs on flexible substrates. .

[Treatment strategy of carotid blowout syndrome after radiotherapy for nasopharyngeal carcinoma].

Objective:To investigate the treatment of internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma. Methods:The clinical data of 7 patients with internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma from March 2020 to March 2023 were retrospectively analyzed. Results:Skull base osteonecrosis with infection occurred in 4 cases, and tumor recurrence with infection in 3 cases. DSA showed that internal carotid artery rupture was located in the internal carotid artery petrosal segment in 6 cases, and in the paravicular segment in 1 case. Balloon occlusion test（BOT） was performed in 6 patients, of which 3 passed and 3 failed. Vascular treatment included internal carotid artery embolization（4 cases）, false aneurysm embolization 1 case（rebleeding）, coated stent 1 case（rebleeding）, muscle compression during operation（1 case）. Patients with rebleeding received high-flow bypass. Three cases developed cerebral infarction after embolization without severe sequelae after treatment, and no death occurred within 90 days. After bleeding control, all 3 patients with cranial base necrosis received surgical treatment to remove the necrotic bone and tissue flap repair, and 1 patient with recurrence received gamma knife and targeted therapy, 1 patient received immune and surgical therapy, and 1 patient received immune and targeted therapy. Conclusion:Rupture and hemorrhage of internal carotid artery after radiotherapy is related to tumor invasion, tissue injury and local infection after radiotherapy. For those caused by tumor invasion, it is recommended to sacrifice the responsible vessels. For those caused by infection, emergency surgery is recommended and blood vessels preserved. Emergency vascular occlusion remains a life-saving option.

High-efficiency single-frequency DBR fiber laser at 1091 nm utilizing a Yb:YAG crystal-derived silica fiber.

A single-frequency distributed Bragg Reflector (DBR) fiber laser operating at 1091 nm was demonstrated by using a Yb:YAG crystal-derived silica fiber (YDSF). The YDSF was prepared via the molten core (MC) method, with a Yb2O3 doping concentration of 5.60 wt.% in the core, resulting in a gain coefficient of 1.45 dB/cm at 1091 nm. Employing 0.8 cm of the YDSF, we attained a single-frequency laser with a maximum output power of 145 mW and a slope efficiency of 31.8%. The laser exhibited an optical signal-to-noise ratio (OSNR) exceeding 71 dB, a linewidth of ∼34 kHz, and a stabilized relative intensity noise (RIN) at -132 dB/Hz for frequencies over 4.5 MHz. The fiber laser could serve as an outstanding seed source for high-power, narrow-linewidth fiber amplifiers operating at 1091 nm.

Secofumitremorgins C and D, a pair of atropisomers from saltern-derived fungus Aspergillus fumigatus GXIMD00544.

A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.

Dual-Locked Fluorescent Probes Activated by Aminopeptidase N and the Tumor Redox Environment for High-Precision Imaging of Tumor Boundaries.

Clear delineation of tumor margins is essential for accurate resection and decreased recurrence rate in the clinic. Fluorescence imaging is emerging as a promising alternative to traditional visual inspection by surgeons for intraoperative imaging. However, traditional probes lack accuracy in tumor diagnosis, making it difficult to depict tumor boundaries accurately. Herein, we proposed an offensive and defensive integration (ODI) strategy based on the "attack systems (invasive peptidase) and defense systems (reductive microenvironment)" of multi-dimensional tumor characteristics to design activatable fluorescent probes for imaging tumor boundaries precisely. Screened out from a series of ODI strategy-based probes, ANQ performed better than traditional probes based on tumor unilateral correlation by distinguishing between tumor cells and normal cells and minimizing false-positive signals from living metabolic organs. To further improve the signal-to-background ratio in vivo, derivatized FANQ, was prepared and successfully applied to distinguish orthotopic hepatocellular carcinoma tissues from adjacent tissues in mice models and clinical samples. This work highlights an innovative strategy to develop activatable probes for rapid diagnosis of tumors and high-precision imaging of tumor boundaries, providing more efficient tools for future clinical applications in intraoperative assisted resection.

Greenhouse covering cultivation promotes chlorophyll accumulation of tea plant (Camellia sinensis) by activating relevant gene expression and enzyme activity.

BACKGROUND: The tea plant (Camellia sinensis (L.) O. Kuntze) is one of the most economically important woody crops. Plastic greenhouse covering cultivation has been widely used in tea areas of northern China. Chlorophyll is not only the crucial pigment for green tea, but also plays an important role in the growth and development of tea plants. Currently, little is known about the effect of plastic greenhouse covering cultivation on chlorophyll in tea leaves. RESULTS: To investigate the effect of plastic greenhouse covering cultivation on chlorophyll in tea leaves, color difference values, chlorophyll contents, gene expression, enzyme activities and photosynthetic parameters were analyzed in our study. Sensory evaluation showed the color of appearance, liquor and infused leaves of greenhouse tea was greener than field tea. Color difference analysis for tea liquor revealed that the value of ∆L, ∆b and b/a of greenhouse tea was significantly higher than field tea. Significant increase in chlorophyll content, intracellular CO2, stomatal conductance, transpiration rate, and net photosynthetic rate was observed in greenhouse tea leaves. The gene expression and activities of chlorophyll-metabolism-related enzymes in tea leaves were also activated by greenhouse covering. CONCLUSION: The higher contents of chlorophyll a, chlorophyll b and total chlorophyll in greenhouse tea samples were primarily due to higher gene expression and activities of chlorophyll-metabolism-related enzymes especially, chlorophyll a synthetase (chlG), pheophorbide a oxygenase (PAO) and chlorophyllide a oxygenase (CAO) in tea leaves covered by greenhouse. In general, our results revealed the molecular basis of chlorophyll metabolism in tea leaves caused by plastic greenhouse covering cultivation, which had great significance in production of greenhouse tea.

The Carthamus tinctorius L. genome sequence provides insights into synthesis of unsaturated fatty acids.

Domesticated safflower (Carthamus tinctorius L.) is a widely cultivated edible oil crop. However, despite its economic importance, the genetic basis underlying key traits such as oil content, resistance to biotic and abiotic stresses, and flowering time remains poorly understood. Here, we present the genome assembly for C. tinctorius variety Jihong01, which was obtained by integrating Oxford Nanopore Technologies (ONT) and BGI-SEQ500 sequencing results. The assembled genome was 1,061.1 Mb, and consisted of 32,379 protein-coding genes, 97.71% of which were functionally annotated. Safflower had a recent whole genome duplication (WGD) event in evolution history and diverged from sunflower approximately 37.3 million years ago. Through comparative genomic analysis at five seed development stages, we unveiled the pivotal roles of fatty acid desaturase 2 (FAD2) and fatty acid desaturase 6 (FAD6) in linoleic acid (LA) biosynthesis. Similarly, the differential gene expression analysis further reinforced the significance of these genes in regulating LA accumulation. Moreover, our investigation of seed fatty acid composition at different seed developmental stages unveiled the crucial roles of FAD2 and FAD6 in LA biosynthesis. These findings offer important insights into enhancing breeding programs for the improvement of quality traits and provide reference resource for further research on the natural properties of safflower.

A novel endolysin from an Enterococcus faecalis phage and application.

Enterococcus faecalis is the primary species detected in cases of secondary persistent infection resulting from root canal therapy failure. Due to the overuse of antibacterial agents, E. faecalis has developed resistance to these drugs, making it challenging to treat clinical diseases caused by E. faecalis infection. Therefore, there is an urgent need to explore new alternative drugs for treating E. faecalis infections. We aimed to clone and express the genes of phage endolysins, purify the recombinant proteins, and analyze their antibacterial activity, lysis profile, and ability to remove biofilm. The crude enzyme of phage endolysin pEF51 (0.715 mg/mL), derived from phage PEf771 infecting E. faecalis, exhibited superior bacterial inhibitory activity and a broader bactericidal spectrum than its parental phage PEf771. Furthermore, pEF51 demonstrated high efficacy in eliminating E. faecalis biofilm. Therapeutic results of the infected Sprague-Dawley (SD) rat model indicated that among 10 SD rats, only one developed a thoracic peritoneal abscess and splenic peritoneal abscess after 72 h of treatment with pEF51. This suggests that pEF51 could provide protection against E. faecalis infection in SD rats. Based on the 16S rDNA metagenomic data of the intestinal microbial community of SD rats, endolysin pEF51 exerted a certain influence on the diversity of intestinal microorganisms at the genus level. Thus, pEF51 may serve as a promising alternative to antibiotics in the management of E. faecalis infection.

Associations of cold-inducible RNA-binding protein with bacterial load, proinflammatory cytokines and mortality from pneumonia.

Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown whether CIRP is strongly associated with bacterial load, inflammatory response, and mortality in sepsis model. Pneumonia was induced in specific pathogen-free 8-9-week old male rats by injecting bacteria via puncture of the tracheal cartilage. The expressions of CIRP and proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß] in lung tissues, alveolar macrophages (AMs), plasma, and bronchoalveolar lavage fluid (BALF) were determined by reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The numbers of bacteria recovered from the lungs were correlated with the bacterial loads injected and mortality. The expressions of CIRP increased sharply as the bacterial loads increased in the lung tissues and AMs. The amounts of TNF-α, IL-6 and IL-1ß proteins synthesized were dependent on the bacterial load in the lung tissues. Releases of CIRP, TNF-α, IL-6, and IL-1ß increased with the bacterial load in the blood plasma. The proteins confirmed similar patterns in the BALF. CIRP was strongly associated with the releases of TNF-α, IL-6, and IL-1ß in the lung tissues, blood plasma, and BALF, and showed a close correlation with mortality. CIRP demonstrated a strong association with bacterial load, which is new evidence, and close correlations with proinflammatory cytokines and mortality of pneumonia in rats, suggesting that it might be an interesting pneumonic biomarker for monitoring host response and predicting mortality, and a promising target for immunotherapy.

Iron modified hydrogen-bonded organic framework as fluorescent sensor for ascorbic acid detection.

Herein, iron modified hydrogen-bonded organic framework (Fe-HOF) was successfully prepared by introducing the yellow-green fluorescent ligand 2,5-dihydroxyterephthalic acid into HOF and then modifying Fe3+. A simple turn-on fluorescence strategy is proposed for the detection of ascorbic acid (AA) based on Fe-HOF. Fe3+ could effectively quench fluorescence emission of HOF. In the presence of AA, Fe3+ was reduced to Fe2+, which led to the fluorescence recovery of HOF, thus realizing the fluorescence quantitative detection of AA. These fluorescence responsive behaviors of Fe-HOF ensure fluorescence assay of AA within 0.5 - 8 µM, along with a limit of detection (LOD) of 0.14 µM. The sensing platform could realize the rapid detection of ascorbic acid in vitamin C pills, tablets and beverages in the detection of ascorbic acid with good recoveries.

Investigation of the regulatory effects of water and nitrogen supply on nitrogen transport and distribution in wolfberry fields.

Resource-based water shortages, uncoordinated irrigation, and fertilization are prevalent challenges in agricultural production. The scientific selection of appropriate water and fertilizer management methods is important for improving the utilization efficiency of agricultural resources and alleviating agricultural non-point source pollution. This study focused on wolfberry and compared the effects of four irrigation levels [full irrigation (W0, 75%-85% θf), slight water deficit (W1, 65%-75% θf), moderate water deficit (W2, 55%-65% θf), and severe water deficit (W3, 45%-55% θf)] and four nitrogen application levels [no nitrogen application (N0, 0 kg·ha-1), low nitrogen application (N1, 150 kg·ha-1), medium nitrogen application (N2, 300 kg·ha-1), and high nitrogen application (N3, 450 kg·ha-1)] on soil nitrate nitrogen (NO3 --N) transport, plant nitrogen allocation, and soil nitrous oxide (N2O) emissions during the harvest period of wolfberry. And this study used CRITIC-entropy weights-TOPSIS model to evaluate 16 water and nitrogen regulation models comprehensively. The results revealed the following: (1) The NO3 --N content of the soil decreased with increasing horizontal distance from the wolfberry. It initially decreased, then increased, and finally decreased with an increase in soil depth. The average NO3 --N content in the 0-100 cm soil layer ranged from 3.95-13.29 mg·kg-1, indicating that W0 > W1, W2, W3, and N3 > N2 > N1 > N0. (2) The soil NO3 --N accumulation ranged from 64.45-215.27 kg·ha-1 under varying water and nitrogen levels, demonstrating a decreasing trend with increasing horizontal distance. The NO3 --N accumulation at each horizontal distance increased with increasing irrigation and nitrogen application. The NO3 --N accumulation of W0N3 treatment increased by 5.55%-57.60% compared with the other treatments. (3) The total nitrogen content and nitrogen uptake in all wolfberry organs were W1 > W0 > W2 > W3, and N2 > N3 > N1 > N0. The maximum total nitrogen content and nitrogen uptake in W1N2 treatment were 3.25% and 27.82 kg·ha-1 in the roots, 3.30% and 57.19 kg·ha-1 in the stems, 3.91% and 11.88 kg·ha-1 in the leaves, and 2.42% and 63.56 kg·ha-1 in the fruits, respectively. (4) The emission flux and total emission of N2O increased with increasing irrigation and nitrogen application. The emission flux exhibited a transient peak (116.39-177.91 ug·m-2·h-1) after irrigation. The intensity of N2O emissions initially decreased and then increased with an increase in the irrigation amount. It also initially increased with increasing nitrogen application amount, then decreased, and finally increased again. The maximum emission intensity was observed under the W3N3 treatment (0.23 kg·kg-1). The N2O emission coefficients ranged from 0.17%-0.39%, in the order of W0 > W1 > W2 > W3 (except for N1) and N1 > N2 > N3. (5) Under varying water and nitrogen concentrations, N2O emission flux showed a positive linear correlation with soil pore water content and NO3 --N content and a negative linear correlation with soil temperature. The comprehensive evaluation revealed that a slight water deficit (65%-75% θf) combined with medium nitrogen application (300 kg·ha-1) decreased soil NO3 --N leaching, increased nitrogen uptake, and reduced N2O emission. These findings can serve as a reference for improving the efficiency and reducing emissions of wolfberry in the Yellow River irrigation region of Gansu Province and in similar climate zones.

Identification and functional analysis of lactic acid metabolism-related differentially expressed genes in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rate that seriously threatens human health. We aimed to investigate the expression, prognostic value, and immune cell infiltration of lactic acid metabolism-related genes (LAMRGs) in HCC using bioinformatics. Methods: The HCC database (The Cancer Genome Atlas-Liver Hepatocellular Carcinoma) was downloaded from the Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) between normal and tumor groups were identified. The LAMRGs were obtained from literature and GeneCards and MSigDB databases. Lactic acid metabolism-related differentially expressed genes (LAMRDEGs) in HCC were screened from the DEGs and LAMRGs. Functional enrichment analyses of the screened LAMRDEGs were further conducted using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The genes were used in multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to construct a prognostic model. Then, a protein-protein interaction network was constructed using STRING and CTD databases. Furthermore, the CIBERSORTx online database was used to assess the relationship between immune cell infiltration and hub genes. Results: Twenty-eight lactic acid metabolism-related differentially expressed genes (LAMRDEGs) were identified. The GO and KEGG analyses showed that the LAMRDEGs were related to the prognosis of HCC. The GSEA indicated that the LAMRDEGs were significantly enriched in tumor related pathways. In the multivariate Cox regression analysis, 14 key genes (E2F1, SERPINE1, GYS2, SPP1, PCK1, CCNB1, CYP2C9, IGFBP3, KDM8, RCAN1, ALPL, FBP1, NQO1, and LCAT) were found to be independent prognostic factors of HCC. Finally, the LASSO and Cox regression analyses showed that six key genes (SERPINE1, SPP1, CCNB1, CYP2C9, NQO1, and LCAT) were associated with HCC prognosis. Moreover, the correlation analyses revealed that the expression of the six key genes were associated with immune infiltrates of HCC. Conclusion: The LAMRDEGs can predict the prognosis and may be associated with immune cells infiltration in patients with HCC. These genes might be the promising biomarkers for the prognosis and treatment of HCC.

Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers.

Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (ΔQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (ΔΔQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (Cmax) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.

Diversity and functional traits of seed endophytes of Dysphania ambrosioides from heavy metal contaminated and non-contaminated areas.

Seed endophytes played a crucial role on host plants stress tolerance and heavy metal (HM) accumulation. Dysphania ambrosioides is a hyperaccumulator and showed strong tolerance and extraordinary accumulation capacities of multiple HMs. However, little is known about its seed endophytes response to field HM-contamination, and its role on host plants HM tolerance and accumulation. In this study, the seed endophytic community of D. ambrosioides from HM-contaminated area (H) and non-contaminated area (N) were investigated by both culture-dependent and independent methods. Moreover, Cd tolerance and the plant growth promoting (PGP) traits of dominant endophytes from site H and N were evaluated. The results showed that in both studies, HM-contamination reduced the diversity and richness of endophytic community and changed the most dominant endophyte, but increased resistant species abundance. By functional trait assessments, a great number of dominant endophytes displayed multiple PGP traits and Cd tolerance. Interestingly, soil HM-contamination significantly increased the percentage of Cd tolerance isolates of Agrobacterium and Epicoccum, but significantly decreased the ration of Agrobacterium with the siderophore production ability. However, the other PGP traits of isolates from site H and N showed no significant difference. Therefore, it was suggested that D. ambrosioides might improve its HM tolerance and accumulation through harboring more HM-resistant endophytes rather than PGP endophytes, but to prove this, more work need to be conducted in the future.