Author Correction: Autophagy maintains tumour growth through circulating arginine.

In this Letter, 'released' should have been 'regulated' in the sentence starting: 'Deletion of Atg5 in the host similarly regulated circulating arginine and suppressed tumorigenesis...' This has been corrected online.

Visible-Light-Promoted Reduction of Nitroarenes with Formate Salts as Reductants.

A visible-light-promoted reduction of nitrobenzenes using formate salts as the reductant was developed. A wide range of nitrobenzenes can be converted into aniline products in a transition metal free fashion. Mechanistic studies revealed that radical species (carbon dioxide radical anion and thiol radical) are key intermediates for the transformation. We anticipate that this method will provide a valuable and green strategy for the reduction of nitrobenzenes.

Autophagy maintains tumour growth through circulating arginine.

Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and to enable survival during starvation1-5. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect that manifests as starvation intolerance and gradual loss of white adipose tissue, liver glycogen and muscle mass1. Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumours in models of autochthonous cancer6,7. Acute, systemic deletion of Atg7 or acute, systemic expression of a dominant-negative ATG4b in mice induces greater regression of KRAS-driven cancers than does tumour-specific autophagy deletion, which suggests that host autophagy promotes tumour growth1,8. Here we show that host-specific deletion of Atg7 impairs the growth of multiple allografted tumours, although not all tumour lines were sensitive to host autophagy status. Loss of autophagy in the host was associated with a reduction in circulating arginine, and the sensitive tumour cell lines were arginine auxotrophs owing to the lack of expression of the enzyme argininosuccinate synthase 1. Serum proteomic analysis identified the arginine-degrading enzyme arginase I (ARG1) in the circulation of Atg7-deficient hosts, and in vivo arginine metabolic tracing demonstrated that serum arginine was degraded to ornithine. ARG1 is predominantly expressed in the liver and can be released from hepatocytes into the circulation. Liver-specific deletion of Atg7 produced circulating ARG1, and reduced both serum arginine and tumour growth. Deletion of Atg5 in the host similarly regulated [corrected] circulating arginine and suppressed tumorigenesis, which demonstrates that this phenotype is specific to autophagy function rather than to deletion of Atg7. Dietary supplementation of Atg7-deficient hosts with arginine partially restored levels of circulating arginine and tumour growth. Thus, defective autophagy in the host leads to the release of ARG1 from the liver and the degradation of circulating arginine, which is essential for tumour growth; this identifies a metabolic vulnerability of cancer.

Protective Effects and Mechanisms of Melatonin on Stress Myocardial Injury in Rats.

ABSTRACT: Prolonged and intense stress can exceed the body's normal self-regulation and limited compensatory and repair capacity, resulting in pathological damage to the body. In this study, we established a rat stress myocardial injury (SMI) model to explore the protective effect of melatonin (MLT) on SMI and its possible mechanisms of action. Adult female Sprague Dawley (SD) rats were randomly divided into 5 groups: blank control group (NC), SMI group, MLT low-dose group, MLT medium-dose group, and MLT high-dose group, and 10 rats in each group were used to establish a SMI model by the water immersion restraint method. We observed the changes in body weight and tail vein glucose of each group. Serum levels of corticosterone (Cort), creatine kinase isoenzyme (CK-MB), and Troponin Ⅰ (Tn-Ⅰ) and activity of lactic acid dehydrogenase were measured by ELISA. Transcriptome sequencing was used to find differentially expressed genes in the control and model groups, and the results were verified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). HE staining was used to visualize the pathological changes in the heart tissue of each group, and Western blot was used to study the differences in protein expression in the cardiomyocytes of each group to further corroborate the results. The body weight growth rate of rats in the SMI group was significantly lower than that of the NC group ( P < 0.01), and the body weight growth rate of rats in the MLT high-dose group was significantly higher than that of the SMI group ( P < 0.05) with no significant difference compared with the NC group rats. The mean blood glucose of rats in the SMI group was significantly higher compared with the NC group ( P < 0.001), while the mean blood glucose of rats in the MLT administration groups was dose-dependently reduced compared with the SMI group. By RNA-seq and bioinformatics tools such as KEGG and Gene ontology, we found that the circadian clock-related genes Ciart , Arnt1 , Per1 , and Dbp were significantly downregulated in the SMI group during water immersion stress, and differentially expressed genes were enriched in the p38MAPK signaling pathway and p53 signaling pathway. Moreover, genes related to inflammation and apoptosis were differentially expressed. ELISA results showed that Cort, CK-MB, and Tn-Ⅰ levels were significantly higher in the SMI group compared with the NC group ( P < 0.01) and melatonin reduced the levels of Cort, CK-MB, and Tn-Ⅰ and decreased lactic acid dehydrogenase activity in rat serum. HE staining results showed that melatonin could attenuate stress-generated myocardial injury. Western blot showed that melatonin reduced the expression of p38MAPK, p53, Bax, and caspase-3 and increased the expression of Bcl-2 protein in rat heart. Melatonin can inhibit myocardial injury caused by water immersion, and its mechanism of action may be related to the regulation of the expression of circadian clock genes such as Ciart , Arnt1 , Per1 , and Dbp ; the inhibition of the expression of proapoptotic proteins such as p38MAPK, p53, Bax, and caspase-3; and the increase of the expression of Bcl-2 antiapoptotic protein.

Bile Acid Homeostasis in a Cholesterol 7α-Hydroxylase and Sterol 27-Hydroxylase Double Knockout Mouse Model.

Bile acids (BAs) are diverse molecules that are synthesized from cholesterol in the liver. The synthesis of BAs has traditionally been shown to occur through two pathways. Cholesterol 7α-hydroxylase (CYP7A1) performs the initial and rate-limiting step in the classical pathway, and sterol 27-hydroxylase (CYP27A1) initiates the hydroxylation of cholesterol in the alternative pathway. While the role of individual BA species as physiological detergents is relatively ubiquitous, their endocrine functions as signaling molecules and roles in disease pathogenesis have been emerging to be BA species-specific. In order to better understand the pharmacologic and toxicologic roles of individual BA species in an in vivo model, we created cholesterol 7α-hydroxylase (Cyp7a1) and sterol 27-hydroxylase (Cyp27a1) double knockout (DKO) mice by cross-breeding single knockout mice (Cyp7a1-/- and Cyp27a1-/- ). BA profiling and quantification by liquid chromatography-mass spectrometry of serum, gallbladder, liver, small intestine, and colon of wild-type, Cyp7a1-/- , Cyp27a1-/- , and DKO mice showed that DKO mice exhibited a reduction of BAs in the plasma (45.9%), liver (60.2%), gallbladder (76.3%), small intestine (88.7%), and colon (93.6%), while maintaining a similar BA pool composition compared to wild-type mice. The function of the farnesoid X receptor (FXR) in DKO mice was lower, revealed by decreased mRNA expression of well-known FXR target genes, hepatic small heterodimer partner, and ileal fibroblast growth factor 15. However, response to FXR synthetic ligands was maintained in DKO mice as treatment with GW4064 resulted in similar changes in gene expression in all strains of mice. Conclusion: We provide a useful tool for studying the role of individual BAs in vivo; DKO mice have a significantly reduced BA pool, have a similar BA profile, and maintained response to FXR activation.

Dysregulation of bile acid homeostasis in parenteral nutrition mouse model.

Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12α-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-α (LXRα) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-α (RORα) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXRα function. Western blot showed significantly reduced nuclear migration of RORα protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver RORα signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD.

[Effect of Comprehensive Protocol of Integrative Medicine on Motor Function, Activity of Daily Living and Quality of Life in Hemiplegia Patients after Stroke].

OBJECTIVE: To explore the effects of integrative medicine (IM) rehabilitation protocolon motor function, activity of daily living, and quality of life (QOL) in hemiplegia patients after stroke. METHODS: Totally 120 patients with post-stroke hemiplegia were allocated to four groups using sealed envalope drawing, i.e., the rehabilitation group, the Chinese medical treatment group, the acupuncture group, and the comprehensive rehabilitation group, 30 cases in each group. Based on routine rehabilitative training, patients in the Chinese medical treatment group, the acupuncture group, and the compre-hensive rehabilitation group received standardized treatment based on syndrome typing, Shi's Consciousness-Restoring Resuscitation acupuncture, Chinese herbs + acupuncture comprehensive rehabilitatino protocol, respectively. The treatmet cycle consisted of 4 weeks with 24-week follow-ups. Fugl-Meyer motor assessment (FMA), Modified Barthel Index (MBI), and Stroke-Specific Quality of Life Scale(SS-QQL), and safety assessment were taken as main effect indices before treatment, at week 4 of treatment, at week 12 and 24 of follow-ups, respectively. RESULTS: There was no statistical difference in FMA score, MBI score, SS-QOL score among the four groups before treatment (P > 0.05). These scores were significantly improved in the four groups at week 4 of treatment, week 12 and 24 of follow-ups, respectively (P < 0.05). Besides, FMA score and SS-QOL score were significantly improved in the comprehensive rehabilitation group at each corresponding time point, as compared with other treatment groups (P < 0.05). CONCLUSIONS: The comprehensive protocol could significantly improve motor function, activity of daily living in hemiplegia patients after stroke, and further improve their QOL. Its effect was better than other single treatment.

FXR silencing in human colon cancer by DNA methylation and KRAS signaling.

Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

Four pins assisted reduction of complex segmental femoral fractures: a technique for closed reduction.

Complex segmental femoral fractures are usually not amenable to closed reduction. The purpose of this study was to evaluate a series of patients who had undergone four pins assisted reduction and intramedullary nail fixation to determine the therapeutic effect of this closed reduction technique. Between December 2010 and January 2013, 15 consecutive patients with segmental femoral fractures were treated with four pins assisted reduction at our hospital. The patient was placed in a supine position on a radiolucent fracture table and a gentle traction was attempted on the limb. Usually, the proximal fracture segment exhibited the typical deformity of flexion, external rotation, and abduction, the middle segment exhibited adduction and distal fracture segment exhibited flexion. Four Schanz pins were placed percutaneously to fix one cortex and did not penetrate into the medullary cavity, and the "T" sharp handles were fixed on the Schanz pins. The fragments were then reduced by reversing the deforming forces for segmental fractures by two assistants. And then, the reduction could be easily achieved and intramedullary nail fixation was performed. Radiographs were evaluated for the quality of the reduction and fracture union. Closed reduction was achieved in all patients using the four pins technology. All 15 fractures united uneventfully. No patient had a rotational malunion or limb length discrepancy at the time of the last follow-up. Thirteen of the fifteen (86.7%) patients had anatomic reduction and two of them (13.3%) had minor varus alignment of 3° and 5°. Knee stiffness was observed in 2 patients and no implant failure was observed. Surgical treatment of complex segmental femoral fractures with four pins assisted reduction and intramedullary nail fixation techniques can result in excellent reductions and a high union rate.

Construction of MOF@COF-derived composites for ratiometric fluorescence detection of water with ultralow background.

A ratiometric sensor with ultralow background is highly desired due to its low environmental influence and high sensitivity. Herein, inspired by the solubility difference of carboxylate in aqueous and organic solvents, we prepared a core-shell structure porous zirconia-covalent organic framework (COF) composite through thermal hydrolysis of UiO-66-COF precursors in organic alkali solution. The ligand 2-aminoterephthalic acids (H2BDC-NH2) of UiO-66 were transformed into 2-aminoterephthalate salts (ATA salts) that existed in zirconium-oxo clusters building units. The composites emitted only yellow emission (597 nm) from the COF in organic solvent due to the insolubility of ATA salts that induce aggregation-caused quenching (ACQ) and the protection of the COF shell. Contrarily, when water was added into mixture, the ATA salts were released into solution and its fluorescence recovered at 446 nm, while the fluorescence of COF was quenched due to the blockage of the intramolecular charge transfer (ICT) process by water. Thus, a high-sensitivity ratiometric fluorescence method is obtained with ultralow background signal and fast response (less than 1 min) for sensing water in organic solvent. We believe that the proposed ratiometric fluorescence sensor based on the zirconia-COF composite will provide the guidance for detection with wide applications.

Synthesis of ß-Silyl Amines via Merging Photoinduced Energy and Hydrogen Atom Transfer in Flow.

The development of efficient methods for synthesizing ß-silyl amines has long been a significant goal in organic synthesis. Previous methods mainly relied on the use of prefunctionalized substrates or special reagents. Herein, we present a visible-light-promoted synthesis approach for ß-silyl amines, utilizing a combination of photoinduced energy and hydrogen atom transfer processes. Using flow chemistry technology, a variety of valuable skeletons, including ß-silyl amines and α-amino esters, can be produced from readily available feedstocks such as hydrosilanes and simple alkanes. Moreover, the strategy's full-process fluidized production capability highlights its potential for industrial-scale manufacturing. Mechanistic studies revealed that oxime esters can act as radical precursors as well as hydrogen atom transfer reagents.

Photocatalytic synthesis of ß-amino acid derivatives from alkenes with alkyl formates.

The aminocarbonylation of alkenes is an efficient approach to synthesize important ß-amino acid motifs. However, simple and convenient methods are still rare. Herein, we present a novel visible-light-mediated controllable three-component radical relay coupling of alkenes, alkyl formates and oxime esters. By the combination of hydrogen atom transfer and energy transfer processes, a series of ß-amino esters could be obtained smoothly in one step under mild conditions. We expect that the approach can complement current methodologies for the synthesis of ß-amino esters.

Comparative Mitogenome of Phylogenetic Relationships and Divergence Time Analysis within Potamanthidae (Insecta: Ephemeroptera).

Potamanthidae belongs to the superfamily Ephemeroidea but has no complete mt genome released in the NCBI (except for two unchecked and one partial mt genome). Since the sister clade to Potamanthidae has always been controversial, we sequenced seven mt genomes of Potamanthidae (two species from Rhoenanthus and five species from Potamanthus) in order to rebuild the phylogenetic relationships of Potamanthidae in this study. The divergence time of Potamanthidae was also investigated by utilizing five fossil calibration points because of the indeterminate origin time. In addition, because Rhoenanthus coreanus and Potamanthus luteus are always in low-temperature environments, we aimed to explore whether these two species were under positive selection at the mt genome level. Amongst the 13 PCGs, CGA was used as the start codon in COX1, whereas other genes conformed to initiating with an ATN start codon. From this analysis, UUA (L), AUU (I), and UUU (F) had the highest usage. Furthermore, the DHU arm was absent in the secondary structure of S1 in all species. By combining the 13 PCGs and 2 rRNAs, we reconstructed the phylogenetic relationship of Potamanthidae within Ephemeroptera. The monophyly of Potamanthidae and the monophyly of Rhoenanthus and Potamanthus were supported in the results. The phylogenetic relationship of Potamanthidae + (Ephemeridae + Polymitarcyidae) was also recovered with a high prior probability. The divergence times of Potamanthidae were traced to be 90.44 Mya (95% HPD, 62.80-121.74 Mya), and the divergence times of Rhoenanthus and Potamanthus originated at approximately 64.77 Mya (95% HPD, 43.82-88.68 Mya), thus belonging to the late Pliocene Epoch or early Miocene Epoch. In addition, the data indicated that R. coreanus was under negative selection and that ATP8 and ND2 in Potamanthidae had a high evolutionary rate.

Widespread photosynthesis reaction centre barrel proteins are necessary for haloarchaeal cell division.

Cell division is fundamental to all cellular life. Most archaea depend on either the prokaryotic tubulin homologue FtsZ or the endosomal sorting complex required for transport for division but neither system has been robustly characterized. Here, we show that three of the four photosynthesis reaction centre barrel domain proteins of Haloferax volcanii (renamed cell division proteins B1/2/3 (CdpB1/2/3)) play important roles in cell division. CdpB1 interacts directly with the FtsZ membrane anchor SepF and is essential for cell division, whereas deletion of cdpB2 and cdpB3 causes a major and a minor division defect, respectively. Orthologues of CdpB proteins are also involved in cell division in other haloarchaea, indicating a conserved function of these proteins. Phylogenetic analysis shows that photosynthetic reaction centre barrel proteins are widely distributed among archaea and appear to be central to cell division in most if not all archaea.

Effectiveness of mHealth App-Based Interventions for Increasing Physical Activity and Improving Physical Fitness in Children and Adolescents: Systematic Review and Meta-Analysis.

BACKGROUND: The COVID-19 pandemic has significantly reduced physical activity (PA) levels and increased sedentary behavior (SB), which can lead to worsening physical fitness (PF). Children and adolescents may benefit from mobile health (mHealth) apps to increase PA and improve PF. However, the effectiveness of mHealth app-based interventions and potential moderators in this population are not yet fully understood. OBJECTIVE: This study aims to review and analyze the effectiveness of mHealth app-based interventions in promoting PA and improving PF and identify potential moderators of the efficacy of mHealth app-based interventions in children and adolescents. METHODS: We searched for randomized controlled trials (RCTs) published in the PubMed, Web of Science, EBSCO, and Cochrane Library databases until December 25, 2023, to conduct this meta-analysis. We included articles with intervention groups that investigated the effects of mHealth-based apps on PA and PF among children and adolescents. Due to high heterogeneity, a meta-analysis was conducted using a random effects model. The Cochrane Risk of Bias Assessment Tool was used to evaluate the risk of bias. Subgroup analysis and meta-regression analyses were performed to identify potential influences impacting effect sizes. RESULTS: We included 28 RCTs with a total of 5643 participants. In general, the risk of bias of included studies was low. Our findings showed that mHealth app-based interventions significantly increased total PA (TPA; standardized mean difference [SMD] 0.29, 95% CI 0.13-0.45; P<.001), reduced SB (SMD -0.97, 95% CI -1.67 to -0.28; P=.006) and BMI (weighted mean difference -0.31 kg/m2, 95% CI -0.60 to -0.01 kg/m2; P=.12), and improved muscle strength (SMD 1.97, 95% CI 0.09-3.86; P=.04) and agility (SMD -0.35, 95% CI -0.61 to -0.10; P=.006). However, mHealth app-based interventions insignificantly affected moderate to vigorous PA (MVPA; SMD 0.11, 95% CI -0.04 to 0.25; P<.001), waist circumference (weighted mean difference 0.38 cm, 95% CI -1.28 to 2.04 cm; P=.65), muscular power (SMD 0.01, 95% CI -0.08 to 0.10; P=.81), cardiorespiratory fitness (SMD -0.20, 95% CI -0.45 to 0.05; P=.11), muscular endurance (SMD 0.47, 95% CI -0.08 to 1.02; P=.10), and flexibility (SMD 0.09, 95% CI -0.23 to 0.41; P=.58). Subgroup analyses and meta-regression showed that intervention duration was associated with TPA and MVPA, and age and types of intervention was associated with BMI. CONCLUSIONS: Our meta-analysis suggests that mHealth app-based interventions may yield small-to-large beneficial effects on TPA, SB, BMI, agility, and muscle strength in children and adolescents. Furthermore, age and intervention duration may correlate with the higher effectiveness of mHealth app-based interventions. However, due to the limited number and quality of included studies, the aforementioned conclusions require validation through additional high-quality research. TRIAL REGISTRATION: PROSPERO CRD42023426532; https://tinyurl.com/25jm4kmf.

Mechanisms of STAT3 activation in the liver of FXR knockout mice.

Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is essential in maintaining bile acid (BA) homeostasis, and FXR(-/-) mice develop cholestasis, inflammation, and spontaneous liver tumors. The signal transducer and activator of transcription 3 (STAT3) is well known to regulate liver growth, and STAT3 is feedback inhibited by its target gene, the suppressor of cytokine signaling 3 (SOCS3). Strong activation of STAT3 was detected in FXR(-/-) mouse livers. However, the mechanism of STAT3 activation with FXR deficiency remains elusive. Wild-type (WT) and FXR(-/-) mice were used to detect STAT3 pathway activation in the liver. In vivo BA feeding or deprivation was used to determine the role of BAs in STAT3 activation, and in vitro molecular approaches were used to determine the direct transcriptional regulation of SOCS3 by FXR. STAT3 was activated in FXR(-/-) but not WT mice. BA feeding increased, but deprivation by cholestyramine reduced, serum inflammatory markers and STAT3 activation. Furthermore, the Socs3 gene was determined as a direct FXR target gene. The elevated BAs and inflammation, along with reduced SOCS3, collectively contribute to the activation of the STAT3 signaling pathway in the liver of FXR(-/-) mice. This study suggests that the constitutive activation of STAT3 may be a mechanism of liver carcinogenesis in FXR(-/-) mice.

Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice.

Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR(-/-) and SHP(-/-) mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR(-/-) mice and therefore, increased SHP expression in FXR(-/-) mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR(-/-) mice with overexpression of SHP in hepatocytes (FXR(-/-)/SHP(Tg)) and determined the contribution of SHP in HCC development in FXR(-/-) mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR(-/-) mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR(-/-) mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver.

Microbial community assembly and functional profiles along the soil-root continuum of salt-tolerant Suaeda glauca and Suaeda salsa.

Developing and planting salt-tolerant plants has become a promising way to utilize saline-alkali land resources and ensure food security. Root-associated microbes of salt-tolerant plants have been shown to promote plant growth and alleviate high salt stress, yet very little is known about the salt resistance mechanisms of core microbes in different niches. This study characterized the microbial community structures, assembly processes, and functional profiles in four root-related compartments of two salt-tolerant plants by amplicon and shotgun metagenomic sequencing. The results showed that both plants significantly altered the microbial community structure of saline soils, with greater microbial alpha diversity in the rhizosphere or rhizoplane compared with bulk soils. Stochastic process dominated the microbial assembly processes, and the impact was stronger in Suaeda salsa than in S. glauca, indicating that S. salsa may have stronger resistance abilities to changing soil properties. Keystone species, such as Pseudomonas in the endosphere of S. glauca and Sphingomonas in the endosphere of S. salsa, which may play key roles in helping plants alleviate salt stress, were identified by using microbial co-occurrence network analysis. Furthermore, the microbiomes in the rhizoplane soils had more abundant genes involved in promoting growth of plants and defending against salt stress than those in bulk soils, especially in salt-tolerant S. salsa. Moreover, microbes in the rhizoplane of S. salsa exhibited higher functional diversities, with notable enrichment of genes involved in carbon fixation, dissimilar nitrate reduction to ammonium, and sulfite oxidation. These findings revealed differences and similarities in the microbial community assembly, functional profiles and keystone species closely related to salt alleviation of the two salt-tolerant plants. Overall, our study provides new insights into the ecological functions and varied strategies of rhizosphere microbes in different plants under salt stress and highlights the potential use of keystone microbes for enhancing salt resistance of plants.

Visible-Light-Promoted Catalyst-Free Oxyarylation and Hydroarylation of Alkenes with Carbon Dioxide Radical Anion.

Visible-light-mediated oxyarylation and hydroarylation of alkenes with aryl halides using formate salts as the reductant and hydrogen source under ambient conditions were developed. These protocols represent rare catalyst-free examples of the realization of such transformations. Using styrenes as substrates, oxyarylation could occur smoothly. Whereas, hydroarylation proceeds employing electron deficient alkenes. Moreover, dehalogenation proceeds successfully in the absence of alkenes. We expected that this method could provide a valuable strategy for the functionalization of aryl halides.

Widespread PRC barrel proteins play critical roles in archaeal cell division.

Cell division is fundamental to all cellular life. Most of the archaea employ one of two alternative division machineries, one centered around the prokaryotic tubulin homolog FtsZ and the other around the endosomal sorting complex required for transport (ESCRT). However, neither of these mechanisms has been thoroughly characterized in archaea. Here, we show that three of the four PRC (Photosynthetic Reaction Center) barrel domain proteins of Haloferax volcanii (renamed Cell division proteins B1/2/3 (CdpB1/2/3)), play important roles in division. CdpB1 interacts directly with the FtsZ membrane anchor SepF and is essential for division, whereas deletion of cdpB2 and cdpB3 causes a major and a minor division defect, respectively. Orthologs of CdpB proteins are also involved in cell division in other haloarchaea. Phylogenetic analysis shows that PRC barrel proteins are widely distributed among archaea, including the highly conserved CdvA protein of the crenarchaeal ESCRT-based division system. Thus, diverse PRC barrel proteins appear to be central to cell division in most if not all archaea. Further study of these proteins is expected to elucidate the division mechanisms in archaea and their evolution.