Climate change intensifies algal biomass resurgence in eutrophic Lake Taihu, China.

Climate change can significantly alter phytoplankton growth and proliferation, which would counteract restoration efforts to control algal blooms. However, the knowledge is limited about the quantitative evaluation of the causal effect of algal biomass resurgence in large shallow lakes where there is no significant improvement after long term lake restoration. Here, a bucket process-based phytoplankton dynamic model is developed to quantify the contributions of climate change and nutrients concentration changes to phytoplankton biomass resurgence after 2014 in hypereutrophic Lake Taihu, China. Compared to 2008-2014, the mean water temperature (WT) and the mean phosphate are higher, the mean photosynthetically active radiation (PAR), the mean total suspended solids (TSS), and the mean dissolved inorganic nitrogen (DIN) are lower, during 2015-2020. Their contribution to algal biomass resurgence during 2015-2020 is WT (+58.7 %), PAR (-2.6 %), TSS (+23.2 %), DIN (-22.1 %) and phosphate (+42.7 %), respectively. Climate change (WT, PAR, and TSS), which contributed +64.9 % to the phytoplankton biomass resurgence, underscores the urgent need to continuously take more effective measures to reduce nutrient emissions to offset the effects of climate change in Lake Taihu and in other eutrophic lakes.

Electroacupuncture Improves Insulin Resistance in Type 2 Diabetes Mice by Regulating Intestinal Flora and Bile Acid.

Introduction: Adjusting internal organs and dredging channel electroacupuncture has a definite effect on type 2 diabetes, but the specific mechanism still needs to be further clarified. This study aims to investigate the effects of electroacupuncture on the gut microbiota and bile acids in db/db mice after the intervention of "adjusting internal organs and dredging channel" and further explore its mechanism of action in treating T2DM. Methods: We used db/db mice as the animal model and db/m mice from the same litter as the blank control group, a total of 4 weeks of intervention were conducted. We evaluated the effectiveness of the "adjusting internal organs and dredging channel" treatment by detecting indicators related to glucose and lipid- metabolism. Detect changes in the gut microbiota of mice in each group using 16SrDNA sequencing technology. The content of bile acids in mouse feces was determined using liquid chromatography mass spectrometry, and the correlation analysis between different bile acids and differential bacterial communities was performed. The expression levels of TGR5 and GLP-1 proteins were measured using the Western blot method. Results: Adjusting internal organs and dredging channel electroacupuncture can improve blood glucose levels in db/db mice, increase the abundance of Firmicutes and Actinobacteria, and increase the content of fecal bile acid pool heavy CA and UDCA. At the same time, it also increased the content of TGR5/GLP1 in the small intestine. Conclusion: Adjusting internal organs and dredging channel electroacupuncture can improve the disorder of glucose and lipid metabolism in db/db mice, regulate the abundance and colony composition of intestinal microbiota in mice, and regulate bile acid metabolism in mice. The interaction between bile acid and intestinal microbiota can also be observed; Mutual influence may play a role in regulating blood sugar together.

Lianhua Qingke ameliorates lipopolysaccharide-induced lung injury by inhibiting neutrophil extracellular traps formation and pyroptosis.

LHQK is a patented Traditional Chinese Medicine (TCM) which is clinically used for acute tracheobronchitis, cough, and other respiratory diseases. Recent studies have proved that LHQK exhibits excellent clinical efficacy in the treatment of acute lung injury (ALI). However, the corresponding mechanisms remain largely unexplored. In this study, we investigated the effects and the underlying mechanisms of LHQK on lipopolysaccharide (LPS)-induced ALI in mice. The pathological examination, inflammatory cytokines assessments, and mucus secretion evaluation indicated that administration of LHQK ameliorated LPS-induced lung injury, and suppressed the secretion of Muc5AC and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1ß) in plasma and BALF. Furthermore, the results of cell-free DNA level showed that LHQK significantly inhibited LPS-induced NETs formation. Western blot revealed that LHQK effectively inhibited LPS-triggered pyroptosis in the lung. In addition, RNA-Seq data analysis, relatively bioinformatic analysis, and network pharmacology analysis revealed that LHQK and relative components may play multiple protective functions in LPS-induced ALI/acute respiratory distress syndrome (ARDS) by regulating multiple targets directly or indirectly related to NETs and pyroptosis. In conclusion, LHQK can effectively attenuate lung injury and reduce lung inflammation by inhibiting LPS-induced NETs formation and pyroptosis, which may be regulated directly or indirectly by active compounds of LHQK.

VOZ1 and VOZ2 transcription factors regulate arsenic tolerance and distribution in rice and Arabidopsis.

Rice is the major source of arsenic (As) intake in humans, as this staple crop readily accumulates As in the grain. Identifying the genes and molecular mechanisms underlying As accumulation and tolerance is a crucial step toward developing rice with reduced As levels. We identified 25 rice genes that improve As tolerance in yeast cells by expressing a complementary DNA (cDNA) library generated from As-treated rice roots. Among them, a zinc finger-type transcription factor VASCULAR PLANT ONE- ZINC FINGER 1 (OsVOZ1) (OsVOZ1) conferred the most pronounced As tolerance. OsVOZ1 inhibits As accumulation in yeast via activation of As efflux transporter Acr3p by post-transcriptional modification in yeast. The Arabidopsis voz1 voz2 double-knockout mutant exhibited As hypersensitivity, altered As concentrations in various tissues, and reduced As transport activity via the phloem. Arabidopsis and rice VOZs were highly expressed in phloem cells in various tissues, which are critical for As distribution in plant tissues. The double-knockdown and single-knockout plants of OsVOZ1 and OsVOZ2 reduced As accumulation in their seeds. These findings suggest that rice and Arabidopsis VOZs regulate the translocation of As into tissues by regulating the phloem loading of this element.

Gold nanorods with iron oxide dual-modal bioprobes in SERS-MRI enable accurate programmed cell death ligand-1 expression detection in triple-negative breast cancer.

The efficiency of immunotherapy for triple-negative breast cancer (TNBC) is relatively low due to the difficulty in accurately detecting immune checkpoints. The detection of TNBC-related programmed cell death ligand-1 (PD-L1) expression is important to guide immunotherapy and improve treatment efficiency. Surface-enhanced Raman spectroscopy (SERS) and magnetic resonance (MR) imaging exhibit great potential for early TNBC diagnosis. SERS, an optical imaging mode, has the advantages of high detection sensitivity, good spatial resolution, and "fingerprint" spectral characteristics; however, the shallow detection penetration of SERS bioprobes limits its application in vivo. MR has the advantages of allowing deep penetration with no radiation; however, its spatial resolution needs to be improved. SERS and MR have complementary imaging features for tumor marker detection. In this study, gold nanorod and ultrasmall iron oxide nanoparticle composites were developed as dual-modal bioprobes for SERS-MRI to detect PD-L1 expression. Anti-PD-L1 (aPD-L1) was utilized to improve the targeting ability and specificity of PD-L1 expression detection. TNBC cells expressing PD-L1 were accurately detected via the SERS imaging mode in vitro, which can image at the single-cell level. In addition, bioprobe accumulation in PD-L1 expression-related tumor-bearing mice was simply and dynamically monitored and analyzed in vivo using MR and SERS. To the best of our knowledge, this is the first time a SERS-MRI dual-modal bioprobe combined with a PD-L1 antibody has been successfully used to detect PD-L1 expression in TNBC. This work paves the way for the design of high-performance bioprobe-based contrast agents for the clinical immunotherapy of TNBC.

Salvianolic acid A diminishes LDHA-driven aerobic glycolysis to restrain myofibroblasts activation and cardiac fibrosis via blocking Akt/GSK-3ß/HIF-1α axis.

Myofibroblasts activation intensively contributes to cardiac fibrosis with undefined mechanism. Salvianolic acid A (SAA) is a phenolic component derived from Salvia miltiorrhiza with antifibrotic potency. This study aimed to interrogate the inhibitory effects and underlying mechanism of SAA on myofibroblasts activation and cardiac fibrosis. Antifibrotic effects of SAA were evaluated in mouse myocardial infarction (MI) model and in vitro myofibroblasts activation model. Metabolic regulatory effects and mechanism of SAA were determined using bioenergetic analysis and cross-validated by multiple metabolic inhibitors and siRNA or plasmid targeting Ldha. Finally, Akt/GSK-3ß-related upstream regulatory mechanisms were investigated by immunoblot, q-PCR, and cross-validated by specific inhibitors. SAA inhibited cardiac fibroblasts-to-myofibroblasts transition, suppressed collage matrix proteins expression, and effectively attenuated MI-induced collagen deposition and cardiac fibrosis. SAA attenuated myofibroblasts activation and cardiac fibrosis by inhibiting LDHA-driven abnormal aerobic glycolysis. Mechanistically, SAA inhibited Akt/GSK-3ß axis and downregulated HIF-1α expression by promoting its degradation via a noncanonical route, and therefore restrained HIF-1α-triggered Ldha gene expression. SAA is an effective component for treating cardiac fibrosis by diminishing LDHA-driven glycolysis during myofibroblasts activation. Targeting metabolism of myofibroblasts might occupy a potential therapeutic strategy for cardiac fibrosis.

Approach-Bias Retraining and Other Training Interventions as Add-On in the Treatment of AUD Patients.

In the past two decades, a variety of cognitive training interventions have been developed to help people overcome their addictive behaviors. Conceptually, it is important to distinguish between programs in which reactions to addiction-relevant cues are trained (varieties of cognitive bias modification, CBM) and programs in which general abilities are trained such as working memory or mindfulness. CBM was first developed to study the hypothesized causal role in mental disorders: by directly manipulating the bias, it was investigated to what extent this influenced disorder-relevant behavior. In these proof-of-principle studies, the bias was temporarily modified in volunteers, either temporarily increased or decreased, with corresponding effects on behavior (e.g., beer consumption), in case the bias was successfully manipulated. In subsequent clinical randomized controlled trials (RCTs), training (away from the substance vs. sham training) was added to clinical treatment. These studies have demonstrated that CBM, as added to treatment, reduces relapse with a small effect of about 10% (similar effect size as for medication, with the strongest evidence for approach-bias modification). This has not been found for general ability training (e.g., working memory training), although effects on other psychological functions have been found (e.g., impulsivity). Mindfulness also has been found to help people overcome addictions, and different from CBM, also as stand-alone intervention. Research on (neuro-)cognitive mechanisms underlying approach-bias modification has pointed to a new perspective in which automatic inferences rather than associations are influenced by training, which has led to the development of a new variety of training: ABC training.

Observation of complications assessed by Clavien-Dindo classification in different endoscopic procedures of benign prostatic hyperplasia: An observational study.

The Clavien-Dindo classification (CDC) was widely used in the assessment of surgical complications, but some inconsistencies always existed in urological literature. This study was aimed to report complications of the transurethral resection of the prostate (TURP), plasmakinetic resection of the prostate (PKRP), and holmium laser enucleation of the prostate (HoLEP) by using a more detailed way under the framework of CDC. A total of 623 eligible cases underwent endoscopic procedures from January 2018 and December 2020 were divided into the TURP group (212 cases), the PKRP group (208 cases), and the HoLEP group (203 cases) according to the surgical type. Patients' surgical complications assessed by the CDC were compared among the 3 groups. The operation time, intraoperative irrigation volume, postoperative irrigation time and volume, decrease in hemoglobin and sodium, postoperative catheterization time, visual analogue scale, hospital stay of the PKEP group and the HoLEP group were significantly less than those of the TURP group, and the decrease in hemoglobin and visual analogue scale in the HoLEP group were significantly lower than those in the PKEP group (all P < .05). The electrolyte disturbance, urinary tract irritation, and patients with grade II of CDC in the PKRP group were significantly lower than those in the TURP group; The electrolyte disturbance, lower abdominal pain, urinary tract irritation, intraoperative hemorrhage, secondary hemorrhage, clot retention, patients with grade I, II, III of CDC in the HoLEP group were significantly lower than those in the TURP group, and the urinary tract irritation, grade I, II of CDC in the HoLEP group was significantly lower than that in the PKRP group (all P < .05). The CDC should be recommended because of the enhanced insight into surgical complications, and the HoLEP should be given a priority for Benign prostatic hyperplasia (BPH) surgical treatment in terms of the merits in surgical characteristics and complications.

Impacts of dietary copper on the swine gut microbiome and antibiotic resistome.

Restrictions on antibiotic growth promoters have prompted livestock producers to use alternative growth promoters, and dietary copper (Cu) supplementation is currently being widely used in pig production. However, elevated doses of dietary Cu constitute a risk for co-selection of antibiotic resistance and the risk may depend on the type of Cu-based feed additives being used. We here report the first controlled experiment investigating the impact of two contrasting Cu-based feed additives on the overall swine gut microbiome and antibiotic resistome. DNA was extracted from fecal samples (n = 96) collected at four time points during 116 days from 120 pigs allotted to three dietary treatments: control, divalent copper sulfate (CuSO4; 250 µg Cu g-1 feed), and monovalent copper oxide (Cu2O; 250 µg Cu g-1 feed). Bacterial community composition, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) were assessed, and bioavailable Cu ([Cu]bio) was determined using whole-cell bacterial bioreporters. Cu supplementation to feed increased total Cu concentrations ([Cu]total) and [Cu]bio in feces 8-10 fold and at least 670-1000 fold, respectively, but with no significant differences between the two Cu sources. The swine gut microbiome harbored highly abundant and diverse ARGs and MGEs irrespective of the treatments throughout the experiment. Microbiomes differed significantly between pig growth stages and tended to converge over time, but only minor changes in the bacterial community composition and resistome could be linked to Cu supplementation. A significant correlation between bacterial community composition (i.e., bacterial taxa present) and ARG prevalence patterns were observed by Procrustes analysis. Overall, results of the experiment did not provide evidence for Cu-induced co-selection of ARGs or MGEs even at a Cu concentration level exceeding the maximal permitted level for pig diets in the EU (25 to 150 µg Cu g-1 feed depending on pig age).

Inhibition Ras/MEK/ERK pathway: An important mechanism of Baihu Jia Guizhi Decoction ameliorated rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alleviating rheumatism by inhibiting synovitis is a routine treatment for rheumatoid arthritis (RA). Baihu Jia Guizhi Decoction (BHJGZ) is a classic prescription and has a long history of application for treating RA with a good anti-inflammatory action. However, the underlying molecular mechanisms have not been fully elucidated. AIM OF THE STUDY: This work aimed to decipher the potential mechanism of BHJGZ against RA focusing on Ras/MEK/ERK pathway. MATERIALS AND METHODS: Based on the prediction of network pharmacology, the inhibition action of BHJGZ on Ras/MEK/ERK pathway was firstly validated in vivo and in vitro. Moreover, the affinity with the ingredients of BHJGZ in serum and the targets of Ras/MEK/ERK pathway were evaluated. Finally, the efficacy of BHJGZ for relieving RA was assessed in AA rats. RESULTS: The Ras/MEK/ERK pathway was predicted by network pharmacology as one of important mechanisms of BHJGZ to treat RA. The high expression of Ras protein in synovitis of AA rats was significantly reduced by the treatment with BHJGZ, and the activation of Ras/MEK/ERK pathway in vivo and in vitro was also markedly inhibited (p < 0.05 or p < 0.01). Moreover, the level of p-ERK/ERK, IL-6 and TNF-α in vitro were further suppressed after Ras or MEK was inhibited by mirdametinib or lonafarnib respectively (p < 0.01). Furthermore, the results of molecular docking showed a good affinity and stable binding with the ingredients of BHJGZ in serum and multiple key proteins of the Ras/MEK/ERK pathway. Finally, paw swelling, paw circumference and pathological changes of joint synovitis were significantly reduced by BHJGZ in AA rats (p < 0.05). CONCLUSION: The inhibition of Ras/MEK/ERK pathway is one of crucial mechanisms of BHJGZ for ameliorating synovitis of RA.