Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study was aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received GnRH antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS: Prostate cancer patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Regulation mechanism and bioactivity characteristic of surfactin homologues with C14 and C15 fatty acid chains.

BACKGROUND: Surfactin, a green lipopeptide bio-surfactant, exhibits excellent surface, hemolytic, antibacterial, and emulsifying activities. However, a lack of clear understanding of the synthesis regulation mechanism of surfactin homologue components has hindered the customized production of surfactin products with different biological activities. RESULTS: In this study, exogenous valine and 2-methylbutyric acid supplementation significantly facilitated the production of C14-C15 surfactin proportions (up to 75% or more), with a positive correlation between the homologue proportion and fortified concentration. Subsequently, the branched-chain amino acid degradation pathway and the glutamate synthesis pathway are identified as critical pathways in regulating C14-C15 surfactin synthesis by transcriptome analysis. Overexpression of genes bkdAB and glnA resulted in a 1.4-fold and 1.3-fold increase in C14 surfactin, respectively. Finally, the C14-rich surfactin was observed to significantly enhance emulsification activity, achieving an EI24 exceeding 60% against hexadecane, while simultaneously reducing hemolytic activity. Conversely, the C15-rich surfactin demonstrated an increase in both hemolytic and antibacterial activities. CONCLUSION: This study presents the first evidence of a potential connection between surfactin homologue synthesis and the conversion of glutamate and glutamine, providing a theoretical basis for targeting the synthesis regulation and structure-activity relationships of surfactin and other lipopeptide compounds.

Ling-Gui-Zhu-Gan decoction protects against doxorubicin-induced myocardial injury by downregulating ferroptosis.

OBJECTIVE: To investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) protects against doxorubicin (DOX)-induced myocardial injury. METHODS: In vivo experiment, rats were divided into six groups: normal group, model group (15 mg/kg, DOX), Dex group(150 mg/kg, Dex), LGZGD-L group (2.1 g/kg), LGZGD-M group (4.2 g/kg), and LGZGD-H group (8.4 g/kg). We used HE and Masson staining to observe the histopathological changes, echocardiography to assess the cardiac function, and western blot and RT-qPCR to detect the expressions of Nrf2, GPX4, Fpn1, and Ptgs2. In vitro experiment, we used immunofluorescence to detect ROS production, and RT-qPCR to detect gene expression of GPX4, Fpn1, and Ptgs2. KEY FINDINGS: In vivo, LGZGD improved cardiac systolic function. LGZGD significantly reduced MDA, LDH, and CK levels, increased SOD activity, enhanced the protein expression of Nrf2, GPX4, and Fpn1, and decreased Ptgs2 levels. In vitro, LGZGD-containing serum significantly reduced ROS, increased the gene expression of GPX4 and Fpn1, and decreased the gene expression of Ptgs2. Furthermore, compared with the LGZGD (si-NC) group, the LGZGD (si-Nrf2) group had decreased gene expression of Nrf2, GPX4, and Fpn1 and increased gene expression of Ptgs2. CONCLUSIONS: LGZGD can ameliorate DOX-cardiotoxicity by activating the Nrf2 signaling pathway and inhibiting ferroptosis in cardiomyocytes.

Associations between gestational weight gain under different guidelines and adverse birth outcomes: A secondary analysis of a randomized controlled trial in rural western China.

Several gestational weight gain (GWG) guidelines have been established based on monocenter or multicenter researches. We aimed to examine the associations between categories of GWG under the Institute of Medicine (IOM) recommendation guideline, the Chinese National Health Commission (NHC) guideline, and weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project and adverse birth outcomes. We used data from an antenatal micronutrient supplementation trial in rural western China between 2002 and 2006. Maternal weekly average GWG during the second and third trimesters was calculated and classified into inadequate, adequate and excessive GWG according to the IOM and NHC, respectively. Weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project were grouped into three subgroups using two approaches: z-score percentile<25th, 25th to 75th, >75th and z-score <-1, -1 to 1, >1 SD. Infant birth weight and gestational age were measured using standard approaches. Generalized linear model with binomial family and logit link was applied to estimate the odds ratio (OR) and 95% confidential intervals (CI) for GWG categories and adverse birth outcomes. Among 1,239 women with normal weight (18.5 kg/m2 to 23.9 kg/m2) during early pregnancy, 18.0% and 34.2% were classified as adequate GWG according to IOM and NHC, respectively. Less than half of Chinese women reached optimal GWG by any recommendation guideline. According to NHC, excessive GWG showed a significant association with macrosomia (OR 3.75, 95% CI 1.03, 13.74), large-for-gestation-age (LGA) (OR 2.12, 95% CI 1.01, 4.45), and inadequate GWG was associated with post-term birth (OR 2.25, 95% CI 1.21, 4.16), compared with adequate GWG. Inappropriate GWG was associated with adverse birth outcomes even among women with normal weight during early pregnancy. The monitoring and interventions of weight status during pregnancy, especially for the second and third trimesters, are of great public health importance for optimal birth outcomes. Additionally, developing guideline of appropriate GWG ranges should account for the traits of regional population.

Biocompatible Ferrofluid-Based Millirobot for Tumor Photothermal Therapy in Near-Infrared-II Window.

Ferrofluidic robots with excellent deformability and controllability have been intensively studied recently. However, most of these studies are in vitro and the use of ferrofluids for in vivo medicinal applications remains a big challenge. The application of ferrofluidic robots to the body requires the solution of many key problems. In this study, biocompatibility, controllability, and tumor-killing efficacy are considered when creating a ferrofluid-based millirobot for in vivo tumor-targeted therapy. For biocompatibility problems, corn oil is used specifically for the ferrofluid robot. In addition, a control system is built that enables a 3D magnetic drive to be implemented in complex biological media. Using the photothermal conversion property of 1064 nm, the ferrofluid robot can kill tumor cells in vitro; inhibit tumor volume, destroy the tumor interstitium, increase tumor cell apoptosis, and inhibit tumor cell proliferation in vivo. This study provides a reference for ferrofluid-based millirobots to achieve targeted therapies in vivo.

Cefiderocol: Clinical application and emergence of resistance.

Antibacterial drug resistance of gram-negative bacteria (GNB) results in high morbidity and mortality of GNB infection, seriously threaten human health globally. Developing new antibiotics has become the critical need for dealing with drug-resistant bacterial infections. Cefiderocol is an iron carrier cephalosporin that achieves drug accumulation through a unique "Trojan horse" strategy into the bacterial periplasm. It shows high antibacterial activity against multidrug-resistant (MDR) Enterobacteriaceae and MDR non-fermentative bacteria. The application of cefiderocol offers new hope for treating clinical drug-resistant bacterial infections. However, limited clinical data and uncertainties about its resistance mechanisms constrain the choice of its therapeutic use. This review aimed to summarize the clinical applications, drug resistance mechanisms, and co-administration of cefiderocol.

Electroacupuncture Activated Impaired Brain Areas and Improved Mental Status and Sleep Quality in Primary Insomnia Patients.

Objective: This study aimed to investigate the specific neurological mechanisms underlying the effects of electroacupuncture at Shenmen (Heart 7) with Neiguan (Pericardium 6) acupoints in patients with primary insomnia (PI). We sought to understand these mechanisms by comparing changes in areaal homogeneity (ReHo) before and after treatment in PI patients and healthy controls (HC). Methods: Between November 2019 and November 2021, we recruited 17 primary insomnia patients (PI group) and 20 matched healthy controls (HC group) as study subjects from Zhaoqing First People's Hospital. Before electroacupuncture treatment, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) assessments. Resting-state magnetic resonance imaging (MRI) scans were conducted before and after two sessions of electroacupuncture at Shenmen and Neiguan acupoints. Results: Before treatment, primary insomnia patients showed higher PSQI (χ2=1.964; P = .017), HAMA (χ2=2.016; P = .027), and HAMD scores (χ2=2.367; P = .013) compared to healthy controls, and increased ReHo values were observed in the left amygdala, bilateral middle temporal gyrus, and left posterior cingulate gyrus in PI patients, while decreased ReHo values were found in the left posterior cingulate gyrus, right middle frontal gyrus, and right precuneus. After treatment, ReHo values increased in the left superior frontal gyrus, right parahippocampal gyrus, and right cingulate gyrus, while they decreased in the left amygdala and right angular gyrus. Primary insomnia disrupts brain areas in the default network, salience network, and parts of the affective cognitive network. Conclusion: Electroacupuncture at Shenmen and Neiguan acupoints partially activated impaired brain areas in patients with primary insomnia, leading to improvements in mental status and sleep quality. This offers a novel perspective for the clinical treatment of primary insomnia.

Integration of mRNA and miRNA analysis reveals the molecular mechanisms of sugar beet (Beta vulgaris L.) response to salt stress.

The continuous increase of saline-alkali areas worldwide has led to the emergence of saline-alkali conditions, which are the primary abiotic stress or hindering the growth of plants. Beet is among the main sources of sugar, and its yield and sugar content are notably affected by saline-alkali stress. Despite sugar beet being known as a salt-tolerant crop, there are few studies on the mechanisms underlying its salt tolerance, and previous studies have mainly delineated the crop's response to stress induced by NaCl. Recently, advancements in miRNA-mRNA network analysis have led to an increased understanding of how plants, including sugar beet, respond to stress. In this study, seedlings of beet variety "N98122" were grown in the laboratory using hydroponics culture and were exposed to salt stress at 40 days of growth. According to the phenotypic adaptation of the seedlings' leaves from a state of turgidity to wilting and then back to turgidity before and after exposure, 18 different time points were selected to collect samples for analysis. Subsequently, based on the data of real-time quantitative PCR (qRT-PCR) of salt-responsive genes, the samples collected at the 0, 2.5, 7.5, and 16 h time points were subjected to further analysis with experimental materials. Next, mRNA-seq data led to the identification of 8455 differentially expressed mRNAs (DEMs) under exposure to salt stress. In addition, miRNA-seq based investigation retrieved 3558 miRNAs under exposure to salt stress, encompassing 887 known miRNAs belonging to 783 families and 2,671 novel miRNAs. With the integrated analysis of miRNA-mRNA network, 57 miRNA-target gene pairs were obtained, consisting of 55 DEMIs and 57 DEMs. Afterwards, we determined the pivotal involvement of aldh2b7, thic, and δ-oat genes in the response of sugar beet to the effect of salt stress. Subsequently, we identified the miRNAs novel-m035-5p and novel-m0365-5p regulating the aldh gene and miRNA novel-m0979-3p regulating the thic gene. The findings of miRNA and mRNA expression were validated by qRT-PCR.

Inhibition of ACLY overcomes cancer immunotherapy resistance via polyunsaturated fatty acids peroxidation and cGAS-STING activation.

Adenosine 5'-triphosphate citrate lyase (ACLY) is a cytosolic enzyme that converts citrate into acetyl-coenzyme A for fatty acid and cholesterol biosynthesis. ACLY is up-regulated or activated in many cancers, and targeting ACLY by inhibitors holds promise as potential cancer therapy. However, the role of ACLY in cancer immunity regulation remains poorly understood. Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Mechanistically, ACLY inhibition causes polyunsaturated fatty acid (PUFA) peroxidation and mitochondrial damage, which triggers mitochondrial DNA leakage to activate the cGAS-STING innate immune pathway. Pharmacological and genetic inhibition of ACLY overcomes cancer resistance to anti-PD-L1 therapy in a cGAS-dependent manner. Furthermore, dietary PUFA supplementation mirrors the enhanced efficacy of PD-L1 blockade by ACLY inhibition. These findings reveal an immunomodulatory role of ACLY and provide combinatorial strategies to overcome immunotherapy resistance in tumors.

Changes in mineral fraction and pore morphology of coal with acidification treatment: contribution of clay minerals to methane adsorption.

The accurate calculation of the contribution which provided by clay minerals in coal on methane adsorption not only bares a significant importance for evaluating the effectiveness of acid stimulation in improving permeability and estimating the coalbed methane reserves but also serves a guide for the governance and utilization of methane resources. In this study, hydrochloric acid (HCl) and hydrofluoric acid (HF) were used to remove specific minerals in Qingdong coal samples. We firstly analyzed the mineral compositions of coal samples with different acidification treatments based on the X-ray diffraction (XRD) experiments, together with analysis of the changes in pore morphology and adsorption capacity. The results showed that acidification did not significantly change the shape of the pores, which remained slit-/plate-like pore. However, the altered adsorption capacity of the coal samples was attributed to changes in pore structure and mineral distribution. Acid erosion of mesopores promoted the transition from mesopores to macropores, contributing to an increase of 8.4% and 24.36% in the percentage of macropores in coal samples treated with HCl and HF, respectively. Fractal dimension D1 grew from 2.2193 to 2.3888 and 2.2572, respectively, but D2 decreased from 2.6146 to 2.5814 and 2.5433, indicating an increment in pore surface roughness and a simplification of the pore structure. The mineral richness of the coal seams should be taken into consideration when applying acid stimulation to increase permeability due to that the acidification products may block the passage of gas migration when the mineral content is slight, which can hinder gas extraction. The aim of this study is to quantitatively determine the contribution rate of clay minerals in coal to methane adsorption with a calculation method is provided by combining pore parameters and limit adsorption capacity, resulting in a contribution rate of 15%.

[Advantages, development opportunities, and practice paths of traditional Chinese medicine in prevention and treatment of elderly comorbidities].

This article focused on the significant public health issue of comorbidities in the elderly population and highlighted the important role of traditional Chinese medicine(TCM) in the prevention and treatment of comorbidities in the elderly. It suggested that TCM should fully utilize its advantages in holistic perspective, syndrome differentiation and treatment, and preventive medicine in the process of preventing and treating comorbidities in the elderly. At the same time, in response to the significant shift in the disease spectrum of the elderly, the increasingly innovative concepts in diagnosis and treatment, the growing demand for proactive health by the el-derly population, and the current emphasis on patient-centered evaluation standards, it is necessary to further conduct basic theoretical and experimental research on comorbidities in the elderly using TCM, emphasize clinical research on comorbidities in the elderly, explore appropriate efficacy evaluation systems, improve TCM prevention and treatment strategies and comprehensive intervention programs for comorbidities in the elderly, and leverage the unique role of TCM in the rehabilitation of elderly comorbidity patients. By analyzing the potential of TCM in the field of comorbidities in the elderly, this article is expected to provide new insights for future clinical practice and scientific research.

Explore the anti-inflammation mechanism of safflower total flavonoids in the treatment of endometritis based on celluar transcriptomics.

OBJECTIVES: Safflower is a traditional Chinese medicine for the treatment of gynecological diseases and its flavonoids have potential anti-inflammatory effects. The purpose is to explore the possible effects of safflower total flavonoids (STF) on lipopolysaccharide (LPS)-induced inflammatory damage of Ishikawa cells. METHOD: In this study, LPS-induced endometrial carcinoma Ishikawa cells were used to establish an inflammatory injury model. The effective concentration of STF was screened by CCK-8 and enzyme-linked immunosorbent assay. The apoptosis of damaged Ishikawa cells was detected by flow cytometry. The contents of caspase11 and caspase 3 in Ishikawa cells were observed by fluorescence imaging. Western blot and RT-qPCR were used to detect the expression of related proteins and mRNA in damaged Ishikawa cells, and the possible mechanism of safflower flavonoids against LPS-induced endometrial carcinoma Ishikawa cells was analyzed by cell transcriptomics. KEY FINDINGS: The STF-reduced tumor necrosis factor α, interleukin-1ß, and interleukin-6 expression level; the expression level of the proteins ASK1, Caspase3, and Caspase11 was also significantly decreased, and the proteins ERα, p-PI3K, and p-AKT were significantly increased. The transcriptome results showed that the PI3K-Akt signal pathway may be the main signal pathway for the STF. CONCLUSION: The STF could regulate the PI3K/AKT signal pathway to treat the inflammatory injury of Ishikawa cells.

Association analysis of agronomic traits and construction of genetic networks by resequencing of 306 sugar beet (Beta vulgaris L.) lines.

Due to the relatively brief domestication history of sugar beet (Beta vulgaris ssp. vulgaris), our understanding of the genomic diversity and functional genes in its cultivars is limited, resulting in slow breeding progress. To address this issue, a total of 306 germplasm materials of major cultivars and breeding lines from China, the USA, and Europe were selected for genome resequencing. We investigated population structure and genetic diversity and performed selective scanning of genomic regions, identifying six novel genes associated with important agronomic traits: the candidate genes DFAX2 and P5CS for skin roughness; the candidate genes FRO5, GL24, and PPR91 for root yield and sugar yield, and the pleiotropic candidate gene POLX for flourishing growth vigour, plant height, crown size, flesh coarseness, and sugar yield. In addition, we constructed a protein-protein interaction network map and a phenotype-gene network map, which provide valuable information for identifying and characterizing functional genes affecting agronomic traits in sugar beet. Overall, our study sheds light on the future improvement of sugar beet agronomic traits at the molecular level.

Dynamic changes in the levels of metabolites and endogenous hormones during the germination of Zanthoxylum nitidum (Roxb.) DC. Seeds.

Accumulating experimental data have shown that endogenous hormones play important roles in regulating seed dormancy and germination. Zanthoxylum nitidum is a medicinal plant that propagates via seeds, which require a long dormancy period for normal germination, and complex changes in metabolites occur during the germination process. However, the regulatory network of endogenous hormones and metabolites during the germination of Z. nitidum seeds remains unclear. This study investigated the dynamic changes in the levels of metabolites and endogenous hormones during the germination of Z. nitidum seeds. The results revealed an increase in the levels of gibberellin 3 (GA3), 12-oxophytodienoic acid (OPDA), 1-aminocyclopropane-1-carboxylic acid (ACC) and trans-zeatin (TZ) and decrease in the levels of abscisic acid (ABA), jasmonic acid (JA), N-[(-)-jasmonoyl]-(S)-isoleucine (JA-Ile) and trans-zeatin riboside (TZR). Overall, 112 differential metabolites (DAMs) were screened from 3 seed samples (Sa, Sb and Sc), most of which are related to primary metabolism. A total of 16 DAMs (including 3 monosaccharides, 3 phosphate lipids, 3 carboxylic acids, 1 amino acid, 2 pyrimidines, and 4 nucleotides) were identified in the three sample comparison pairs (Sa vs Sb, Sa vs Sc, and Sb vs Sc); these DAMs were significantly enriched in purine metabolism; glycerophospholipid metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism and pyruvate metabolism. OPDA, ACC and GAs were significantly positively correlated with upregulated metabolites, whereas ABA and JA were significantly positively correlated with downregulated metabolites. Finally, a hypothetical metabolic network of endogenous hormones that regulate seed germination was constructed. This study deepens our understanding of the importance of endogenous hormonal profiles that mediate seed germination.

[Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS].

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 µm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

TNF-α promotes CXCL-1/8 production in keratinocytes by downregulating galectin-3 through NF-κB and hsa-miR-27a-3p pathway to contribute psoriasis development.

OBJECTIVE: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression. METHODS: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction. RESULTS AND DISCUSSION: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis. CONCLUSION: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.

Current research trends, hotspots, and frontiers of medical nutrition therapy on cancer: a bibliometric analysis.

Background: There is a high prevalence of malnutrition in cancer patients, which seriously affects the anti-cancer therapy effect and outcomes, causing a huge disease burden worldwide. Appropriate nutritional support is important for cancer prevention and control. The aim of this study was to explore the development trends, hotspots, and frontiers of Medical Nutrition Therapy (MNT) on Cancer from a bibliometric perspective, and provide new insights for future research and clinic practices. Methods: The global literature of MNT on Cancer published between 1975 and 2022 were searched in the Web of Science Core Collection Database (WOSCC). After refining the data, descriptive analysis and data visualization were performed with bibliometric tools (CiteSpace, VOSviewer, and R package "bibliometrix"). Results: A total of 10,339 documents with a timespan from 1982 to 2022 were included in this study. The number of documents had increased continuously over the past 40 years, especially with a steep rise from 2016 to 2022. The majority of scientific production outputs were from the United States, which had the most core research institutions and authors. The published documents could be clustered into three themes respectively labeled by terms "double-blind", "cancer" and "quality-of-life". "gastric cancer", "outcome", "inflammation", "sarcopenia" and "exercise" were the most prominent keywords in recent years. "breast-cancer", "colorectal-cancer", "expression", "risk", "in-vitro", "quality-of-life", "cancer" and "life" might represent the newly emerged topics. Conclusions: There were a good research foundation and reasonable disciplinary structure in the field of medical nutrition therapy for cancer at present. The core research team was mainly located in the United States, England, and other developed countries. According to the current trends in publications, more articles shall be published in the future. Nutritional metabolism, malnutrition risk, and the impact of nutritional therapy on prognosis might be research hotspots. In particular, it was important to focus on specific cancer, such as breast cancer, colorectal cancer, and gastric cancer, which might be the frontiers.

Rapid on-site detection of underground petroleum pipeline leaks and risk assessment using portable gas chromatography-mass spectrometry and solid phase microextraction.

Locating underground pipeline leaks can be challenging due to their hidden nature and variable terrain conditions. To sample soil gas, solid-phase microextraction (SPME) was employed, and a portable gas chromatography/mass spectrometry (GC/MS) was used to detect the presence and concentrations of petroleum hydrocarbon volatile organic compounds (pH-VOCs), including benzene, toluene, ethylbenzene, and xylene (BTEX). We optimized the extraction method through benchtop studies using SPME. The appropriate fibre materials and exposure time were selected for each BTEX compound. Before applying SPME, we preconditioned the soil vapour samples by keeping the temperature at around 4 °C and using ethanol as a desorbing agent and moisture filters to minimize the impact of moisture. To conduct this optimisation, airbags were applied to condition the soil vapour samples and SPME sampling. By conditioning the samples using this method, we were able to improve analytical efficiency and accuracy while minimizing environmental impacts, resulting in more reliable research data in the field. The study employed portable GC/MS data to assess the concentration distribution of BTEX in soil vapour samples obtained from 1.5 m below the ground surface at 10 subsurface vapour monitoring locations at the leak site. After optimization, the detection limits of BTEX were almost 100 µg/m3, and the measurement repeatabilities were approximately 5% and 15% for BTEX standards in the laboratory and soil vapour samples in the field, respectively. The soil vapour samples showed a hotspot region with high BTEX concentrations, reaching 30 mg/m3, indicating a diesel return pipeline leak caused by a gasket failure in a flange. The prompt detection of the leak source was critical in minimizing environmental impact and worker safety hazards.

Engineering Streptomyces albulus to enhance ε-poly-L-lysine production by introducing a polyphosphate kinase-mediated ATP regeneration system.

BACKGROUND: ε-Poly-L-lysine (ε-PL) is a natural and safe food preservative that is mainly produced by filamentous and aerobic bacteria Streptomyces albulus. During ε-PL biosynthesis, a large amount of ATP is used for the polymerization of L-lysine. A shortage of intracellular ATP is one of the major factors limiting the increase in ε-PL production. In previous studies, researchers have mainly tried to increase the oxygen supply to enhance intracellular ATP levels to improve ε-PL production, which can be achieved through the use of two-stage dissolved oxygen control, oxygen carriers, heterologous expression of hemoglobin, and supplementation with auxiliary energy substrates. However, the enhancement of the intracellular ATP supply by constructing an ATP regeneration system has not yet been considered. RESULTS: In this study, a polyphosphate kinase (PPK)-mediated ATP regeneration system was developed and introduced into S. albulus to successfully improve ε-PL production. First, polyP:AMP phosphotransferase (PAP) from Acinetobacter johnsonii was selected for catalyzing the conversion of AMP into ADP through an in vivo test. Moreover, three PPKs from different microbes were compared by in vitro and in vivo studies with respect to catalytic activity and polyphosphate (polyP) preference, and PPK2Bcg from Corynebacterium glutamicum was used for catalyzing the conversion of ADP into ATP. As a result, a recombinant strain PL05 carrying coexpressed pap and ppk2Bcg for catalyzing the conversion of AMP into ATP was constructed. ε-PL production of 2.34 g/L was achieved in shake-flask fermentation, which was an increase of 21.24% compared with S. albulus WG608; intracellular ATP was also increased by 71.56%. In addition, we attempted to develop a dynamic ATP regulation route, but the result was not as expected. Finally, the conditions of polyP6 addition were optimized in batch and fed-batch fermentations, and the maximum ε-PL production of strain PL05 in a 5-L fermenter was 59.25 g/L by fed-batch fermentation, which is the highest ε-PL production reported in genetically engineered strains. CONCLUSIONS: In this study, we proposed and developed a PPK-mediated ATP regeneration system in S. albulus for the first time and significantly enhanced ε-PL production. The study provides an efficient approach to improve the production of not only ε-PL but also other ATP-driven metabolites.