Triacylglycerol lipase, OsSG34, plays an important role in grain shape and appearance quality in rice.

Optimal grain-appearance quality is largely determined by grain size. To date, dozens of grain size-related genes have been identified. However, the regulatory mechanism of slender grain formation is not fully clear. We identified the OsSG34 gene by map-based cloning. A 9-bp deletion on 5'-untranslated region of OsSG34, which resulted in the expression difference between the wild-type and sg34 mutant, led to the slender grains and good transparency in sg34 mutant. OsSG34 as an α/ß fold triacylglycerol lipase affected the triglyceride content directly, and the components of cell wall indirectly, especially the lignin between the inner and outer lemmas in rice grains, which could affect the change in grain size by altering cell proliferation and expansion, while the change in starch content and starch granule arrangement in endosperm could affect the grain-appearance quality. Moreover, the OsERF71 was identified to directly bind to cis-element on the mutant site, thereby regulating the OsSG34 expression. Knockout of three OsSG34 homologous genes resulted in slender grains as well. The study demonstrated OsSG34, involved in lipid metabolism, affected grain size and quality. Our findings suggest that the OsSG34 gene could be used in rice breeding for high yield and good grain-appearance quality via marker-assisted selection and gene-editing approaches.

Adipose Triglyceride Lipase-Mediated Adipocyte Lipolysis Exacerbates Acute Pancreatitis Severity in Mouse Models and Patients.

Dyslipolysis of adipocytes has played a critical role in various diseases. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme in adipocyte autonomous lipolysis. However, whether the degree of adipocyte lipolysis relates to the prognoses in acute pancreatitis (AP) and the role of ATGL-mediated lipolysis in the pathogenesis of AP remain elusive. The visceral adipose tissue consumption rate in the acute stage was measured in both patients with AP and mouse models. Lipolysis levels and ATGL expression were detected in caerulein-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, atglistatin, was used in C57Bl/6N and ob/ob AP models. This study found that increased visceral adipose tissue consumption rate in the acute phase was independently associated with adverse prognoses in patients with AP, which was validated in mice AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis could aggravate AP. Genetic blockage of ATGL specifically in adipocytes was able to alleviate the damage to AP. The application of atglistatin could effectively protect against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP.

Silver-Coordinated Watson-Crick Pairing-Driven Three-Dimensional DNA Walker for Locus-Specific Detection of Genomic N6-Methyladenine and N4-Methylcytosine at the Single-Molecule Level.

N6-Methyladenine (6mdA) and N4-methylcytosine (4mdC) are the two most dominant DNA modifications in both prokaryotes and eukaryotes, but standard hybridization-based techniques cannot be applied for the 6mdA/4mdC assay. Herein, we demonstrate the silver-coordinated Watson-Crick pairing-driven three-dimensional (3D) DNA walker for locus-specific detection of genomic 6mdA/4mdC at the single-molecule level. 6mdA-DNA and 4mdC-DNA can selectively hybridize with the binding probes (BP1 and BP2) to form 6mdA-DNA-BP1 and 4mdC-DNA-BP2 duplexes. The 6mdA-C/4mdC-A mismatches cannot be stabilized by AgI, and thus, 18-nt BP1/BP2 cannot be extended by the catalysis of KF exonuclease. Through toehold-mediated strand displacement (TMSD), the signal probe (SP1/SP2) functionalized on the gold nanoparticles (AuNPs) can competitively bind to BP1/BP2 in 6mdA-DNA-BP1/4mdC-DNA-BP2 duplex to obtain SP1-18-nt BP1 and SP2-18-nt BP2 duplexes. The resulting DNA duplexes can act as the substrates of lambda exonuclease, leading to the cleavage of SP1/SP2 and the release of Cy3/Cy5 and 18-nt BP1/BP2. The released 18-nt BP1/BP2 can subsequently serve as the walker DNA, moving along the surface of the AuNP to activate dynamic 3D DNA walking and releasing abundant Cy3/Cy5. The released Cy3/Cy5 can be quantified by single-molecule imaging. This nanosensor exhibits high sensitivity with a limit of detection (LOD) of 9.80 × 10-15 M for 6mdA-DNA and 9.97 × 10-15 M for 4mdC-DNA. It can discriminate 6mdA-/4mdC-DNA from unmodified genomic DNAs, distinguish 0.01% 6mdA-/4mdC-DNA from excess unmethylated DNAs, and quantify 6mdA-/4mdC-DNA at specific sites in genomic DNAs of liver cancer cells and Escherichia coli plasmid cloning vector, providing a new platform for locus-specific analysis of 6mdA/4mdC in genomic DNAs.

Transient Zwitterions Dynamics Empowered Adaptive Interface for Ultra-Stable Zn Plating/Stripping.

A highly reversible zinc anode is crucial for the commercialization of zinc-ion batteries. However, the change in the microstructure of the electric double layer originated from the dynamic change in charge density on the electrode greatly impacts anode reversibility during charge/discharge, which is rarely considered in previous research. Herein, the zwitterion additive is employed to create an adaptive interface by coupling the transient zwitterion dynamics upon the change of interfacial charge density. Ab initio molecular dynamics simulations suggest the molecular orientation and adsorption groups of zwitterions will be determined by the charging state of the electrode. ZnSO4 electrolyte with zwitterion fulfills a highly reversible Zn anode with an average Coulombic efficiency of up to 99.85%. Zn/Zn symmetric cells achieve greatly enhanced cycling stability for 700 h with extremely small voltage hysteresis of 29 mV under 5 mA cm-2 with 5 mAh cm-2 . This study validates the adaptive interface based on transient dynamics of zwitterions, which sheds new light on developing highly reversible metal anodes with a high utilization rate.

Chlamydia trachomatis enhances HPV persistence through immune modulation.

Chlamydia trachomatis (CT) is the most common sexually transmitted infections globally, and CT infection can enhance HPV persistence. Epidemiological analysis has shown that patients with CT/HPV coinfection have a higher risk of developing cervical cancer and exhibit more rapid progression to cervical cancer than patients with HPV infection alone. However, the mechanism has not been fully elucidated. Here, we report that CT infection supports HPV persistence by further suppressing the functions of Langerhans cells (LCs); in particular, CT further activates the PI3K pathway and inhibits the MAPK pathways in LCs, and these pathways are frequently involved in the regulation of immune responses. CT/HPV coinfection also impairs LC functions by reducing the antigen-presenting ability and density of LCs. Moreover, CT/HPV coinfection can alter T-cell subsets, resulting in fewer CD4 + and CD8 + T cells and more infiltrating Tregs. Moreover, CT/HPV coinfection decreases the CD4 + /CD8 + T cell ratio to below 1, coinfection also induces greater T lymphocytes' apoptosis than HPV infection, thus impairing cell-mediated immunity and accelerating the progress to cervical cancer.

Poly (lactic-co-glycolic acid)-encapsulated Endostar-loaded calcium phosphate cement as anti-tumor bone cement for the treatment of bone metastasis in lung cancer.

Lung cancer is one of the most common malignant tumors in the world. In approximately 30%-40% of lung cancer patients, bone metastases ensues with osteolytic destruction. Worse still, intractable pain, pathological fracture, and nerve compression caused by bone metastases are currently the bottleneck of research, diagnosis, and treatment of lung cancer. Therefore, the present study aims at investigating the effectiveness of a new composite material made of calcium phosphate cement (CPC) and Endostar on repairing bone defects in vitro and in vivo. As indicated in results, the mechanical properties of CPC+Endostar and CPC+PLGA+Endostar do not differ from those of pure CPC. The PLGA-embedded Endostar slow-release microspheres were designed and prepared, and were combined with CPC. Poly (lactic-co-glycolic acid (PLGA) is a biodegradable polymer material in vivo, so the effect on its mechanical properties is negligible. CPC+Endostar and CPC+PLGA+Endostar have been proved to inhibit cell proliferation, promote apoptosis and block cell cycle in G2 phase; the expression levels of osteoclast-related genes CXCL2, TGF-ß1, IGF-1, IL-6, and RANKL were significantly decreased while osteogenic ability and alkaline phosphatase activity observably enhanced. In vivo studies have revealed that the expression levels of TRAP, RANKL, and Caspase3 in CPC+PLGA+ENDO-treated tumor tissues after 3 weeks were higher than those in other groups with the prolongation of animal treatment time, while the expression levels of OPN and BCL2 were lower than those in other groups. In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.

Specific Adsorption-Oxidation Strategy in Cathode Inner Helmholtz Plane Enabling 4.6 V Practical Lithium-Ion Full Cells.

Increasing the cutoff voltage effectively maximizes the available capacity of the state-of-art layered-oxide cathodes (LiTMO2). However, the spontaneous dehydrogenation-oxidation of carbonates in the cathode inner Helmholtz plane (C-IHP) under high voltage/temperature leads to side effects, including weak cathode electrolyte interphase (CEI) and cathode structural collapse. Here, we report a specific adsorption-oxidation (Ad-O) mechanism that dominates the later CEI formation through molecular regulation in C-IHP. The two tailored additives with specific electron-rich groups will enter the C-IHP and mask the active sites of cathodes, thereby reducing the weak CEI generation from conventional carbonates. As-formed hierarchical CEI with inner LiF and outer B-F/-CN rich organic structure will further protect the aggressive cathode from harmful electrolyte corrosion under harsh conditions of high voltages (4.6 V) and elevated temperatures (60 °C). This synergistic strategy guided by the specific Ad-O mechanism enables 3.5 Ah LiNi0.8Co0.1Mn0.1O2/Graphite pouch cells, which remarkably achieve 270 Wh/kg with 450 cycles.

Highly Conductive Imidazolate Covalent Organic Frameworks with Ether Chains as Solid Electrolytes for Lithium Metal Batteries.

Poly(ethylene oxide) (PEO)-based electrolytes are often used for Li+ conduction as they can dissociate the Li salts efficiently. However, high entanglement of the chains and lack of pathways for rapid ion diffusion limit their applications in advanced batteries. Recent developments in ionic covalent organic frameworks (iCOFs) showed that their highly ordered structures provide efficient pathways for Li+ transport, solving the limitations of traditional PEO-based electrolytes. Here, we present imidazolate COFs, PI-TMEFB-COFs, having methoxyethoxy chains, synthesized by Debus-Radziszewski multicomponent reactions and their ionized form, Li+@PI-TMEFB-COFs, showing a high Li+ conductivity of 8.81 mS cm-1 and a transference number of 0.974. The mechanism for such excellent electrochemical properties is that methoxyethoxy chains dissociate LiClO4, making free Li+, then those Li+ are transported through the imidazolate COFs' pores. The synthesized Li+@PI-TMEFB-COFs formed a stable interface with Li metal. Thus, employing Li+@PI-TMEFB-COFs as the solid electrolyte to assemble LiFePO4 batteries showed an initial discharge capacity of 119.2 mAh g-1 at 0.5 C, and 82.0 % capacity and 99.9 % Coulombic efficiency were maintained after 400 cycles. These results show that iCOFs with ether chains synthesized via multicomponent reactions can create a new chapter for making solid electrolytes for advanced rechargeable batteries.

Del Nido cardioplegia or potassium induces Nrf2 and protects cardiomyocytes against oxidative stress.

Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We addressed here whether cardioplegia essential for cardiopulmonary bypass surgery activates Nrf2, a transcription factor regulating the expression of antioxidant and detoxification genes. With commonly used cardioplegic solutions, high K+, low K+, Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), and Celsior (CS), we found that DN caused a significant increase of Nrf2 protein in AC16 human cardiomyocytes. Tracing the ingredients in DN led to the discovery of KCl at the concentration of 20-60 mM capable of significant Nrf2 protein induction. The antioxidant response element (ARE) luciferase reporter assays confirmed Nrf2 activation by DN or KCl. Transcriptomic profiling using RNA-seq revealed that oxidation-reduction as a main gene ontology group affected by KCl. KCl indeed elevated the expression of classical Nrf2 downstream targets, including TXNRD1, AKR1C, AKR1B1, SRXN1, and G6PD. DN or KCl-induced Nrf2 elevation is Ca2+ concentration dependent. We found that KCl decreased Nrf2 protein ubiquitination and extended the half-life of Nrf2 from 17.8 to 25.1 mins. Knocking out Keap1 blocked Nrf2 induction by K+. Nrf2 induction by DN or KCl correlates with the protection against reactive oxygen species generation or loss of viability by H2O2 treatment. Our data support that high K+ concentration in DN cardioplegic solution can induce Nrf2 protein and protect cardiomyocytes against oxidative damage.NEW & NOTEWORTHY Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We report here that Del Nido cardioplegic solution or potassium is an effective inducer of Nrf2 transcription factor, which controls the antioxidant and detoxification response. This indicates that Del Nido solution is not only essential for open heart surgery but also exhibits cardiac protective activity.

n-Hexane Diluted Electrolyte with Ultralow Density enables Li-S Pouch Battery Toward >400 Wh kg-1.

Lithium-sulfur (Li-S) batteries are attractive candidates for next generation energy storage devices due to their high theoretical energy density of up to 2600 Wh kg-1 . However, the uneven deposition of lithium, the undesired shuttle of lithium polysulfides (LiPSs), and the excess weight fraction of electrolyte severely impair the practical energy density of Li-S batteries. Here, a low concentrated and nonpolar n-hexane (NH)-diluted electrolyte (named as LCDE) with ultralow-density to alleviate the above dilemmas is proposed. The nonpolar NH boosts the diffusion of lithium ion in LCDE, favoring the homogeneous deposition of lithium. This nonpolar effect also reduces the solubilities of LiPSs, promoting a quasi-solid-state transformation of sulfur chemistry, thus tremendously eradicating the shuttle of LiPSs. Most importantly, the ultra-light NH diluent enables the LCDE with an ultralow density of only 0.79 g mL-1 , which reduces the weight of LCDE by 32.5% compared with conventional ether-based electrolyte. Owing to all the merits, the Li-S pouch cell achieves a high energy density up to 417 Wh kg-1 . The nonpolar NH-diluted electrolyte with multifunction presented in this work provides a new and feasible direction to increase the practical energy density of Li-S batteries.

2D Layered Materials for Fast-Charging Lithium-Ion Battery Anodes.

The development of electric vehicles has received worldwide attention in the background of reducing carbon emissions, wherein lithium-ion batteries (LIBs) become the primary energy supply systems. However, commercial graphite-based anodes in LIBs currently confront significant difficulty in enduring ultrahigh power input due to the slow Li+ transport rate and the low intercalation potential. This will, in turn, cause dramatic capacity decay and lithium plating. The 2D layered materials (2DLMs) recently emerge as new fast-charging anodes and hold huge promise for resolving the problems owing to the synergistic effect of a lower Li+ diffusion barrier, a proper Li+ intercalation potential, and a higher theoretical specific capacity with using them. In this review, the background and fundamentals of fast-charging for LIBs are first introduced. Then the research progress recently made for 2DLMs used for fast-charging anodes are elaborated and discussed. Some emerging research directions in this field with a short outlook on future studies are further discussed.

Mesophilic Argonaute-Based Single Polystyrene Sphere Aptamer Fluorescence Platform for the Multiplexed and Ultrasensitive Detection of Non-Nucleic Acid Targets.

The rapid, simultaneous, and accurate identification of multiple non-nucleic acid targets in clinical or food samples at room temperature is essential for public health. Argonautes (Agos) are guided, programmable, target-activated, next-generation nucleic acid endonucleases that could realize one-pot and multiplexed detection using a single enzyme, which cannot be achieved with CRISPR/Cas. However, currently reported thermophilic Ago-based multi-detection sensors are mainly employed in the detection of nucleic acids. Herein, this work proposes a Mesophilic Argonaute Report-based single millimeter Polystyrene Sphere (MARPS) multiplex detection platform for the simultaneous analysis of non-nucleic acid targets. The aptamer is utilized as the recognition element, and a single millimeter-sized polystyrene sphere (PSmm ) with a large concentration of guide DNA on the surface served as the microreactor. These are combined with precise Clostridium butyricum Ago (CbAgo) cleavage and exonuclease I (Exo I) signal amplification to achieve the efficient and sensitive recognition of non-nucleic acid targets, such as mycotoxins (<60 pg mL-1 ) and pathogenic bacteria (<102 cfu mL-1 ). The novel MARPS platform is the first to use mesophilic Agos for the multiplex detection of non-nucleic acid targets, overcoming the limitations of CRISPR/Cas in this regard and representing a major advancement in non-nucleic acid target detection using a gene-editing-based system.

A Dynamically Stable Sulfide Electrolyte Architecture for High-Performance All-Solid-State Lithium Metal Batteries.

All-solid-state batteries employing sulfide solid electrolyte and Li metal anode are promising because of their high safety and energy densities. However, the interface between Li metal and sulfides suffers from catastrophic instability which stems the practical use. Here, a dynamically stable sulfide electrolyte architecture to construct the hierarchy of interface stability is reported. By rationally designing the multilayer structures of sulfide electrolytes, the dynamic decomposing-alloying process from MS4 (M = Ge or Sn) unit in sulfide interlayer can significantly prohibit Li dendrite penetration is revealed. The abundance of highly electronic insulating decompositions, such as Li2 S, at the sulfide interlayer interface helps to well constrain the dynamic decomposition process and preserve the long-term polarization stability is also highlighted. By using Li6 PS5 Cl||Li10 SnP2 S12 ||Li6 PS5 Cl electrolyte architecture, Li metal anode shows an unprecedented critical current density over 3 mA cm-2 and achieves the steady over-potential for ≈900 hours. Based upon the merits, the Li||LiNi0.8 Co0.1 Mn0.1 O2 battery delivers a remarkable 75.3% retention even after 600 cycles at 1 C (1C-0.95 mA cm-2 ) under a low stack pressure of 15 MPa.

Consistent neutralization of circulating omicron sub-variants by hybrid immunity up to 6 months after booster vaccination.

The current COVID-19 vaccination program requires frequent booster vaccination to maintain sufficient neutralization levels against immune evasive SARS-CoV-2 variants. However, prior studies found more potent and durable immune response in convalescing individuals, raising the possibility of less frequent booster vaccination for them. Here, we conducted a longitudinal immunological study based on two prospective cohorts of booster vaccinated convalescing COVID-19 patients or healthcare workers (HCW) without COVID-19 history in Xiangyang, China. Comparing to 1-month post-boosting, pseudovirus neutralization titers (pVNT50) of ancestral Wuhan-Hu-1 and circulating omicron sub-variants BA.5, BF.7, BA.4.6, BA.2.75, and BA.2.75.2 spikes were stable or even increased in convalescing samples at 6-month post-boosting, when HCW samples showed substantial drop of neutralization titers across the spectrum. Variant-to-Wuhan-Hu-1 pVNT50 ratios showed no significant variation during the 17 months from pre-vaccination to 6-month post-boosting in convalescing individuals, indicating that the high durability of hybrid immunity was likely sustained by continuously improving neutralization potency that compensated immune decay. Our data provide mechanistic insight into prior epidemiological findings that vaccine-elicited humoral immune response was more durable in convalescing individuals than those without SARS-CoV-2 infection, and suggest further research into potential extension of boosting intervals for convalescing individuals.

Changes in root hydraulic conductivity in wheat (Triticum aestivum L.) in response to salt stress and day/night can best be explained through altered activity of aquaporins.

Salt stress reduces plant water flow during day and night. It is not known to which extent root hydraulic properties change in parallel. To test this idea, hydroponically grown wheat plants were grown at four levels of salt stress (50, 100, 150 and 200 mM NaCl) for 5-8d before harvest (d14-18) and subjected to a range of analyses to determine diurnal changes in hydraulic conductivity (Lp) at cell, root and plant level. Cell pressure probe analyses showed that the Lp of cortex cells was differentially affected by salt stress during day and night, and that the response to salt stress differed between the main axis of roots and lateral roots. The Aquaporin (AQP) inhibitor H2 O2 reduced Lp to a common, across treatments, level as observed in salt-stressed plants during the night. Analyses of transpiring plants and exuding root systems provided values of root Lp which were in the same range as values modeled based on cell-Lp. The results can best be explained through a change in root Lp in response to salt stress and day/night, which results from an altered activity of AQPs. qPCR gene expression analyses point to possible candidate AQP isoforms.

Diurnal changes in apoplast bypass flow of water and ions in salt-stressed wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.).

The aim of the present study was to quantify the contribution of apoplastic bypass flow to the uptake of water and salt across the root cylinder of wheat and barley during day and night. Plants were grown on hydroponics until they were 14-17 days old and then analysed over a single day (16 h) or night (8 h) period while being exposed to different concentrations of NaCl (50, 100, 150 and 200 mM NaCl). Exposure to salt started just before the experiment (short-term stress) or had started 6d before (longer-term stress). Bypass flow was quantified using the apoplastic tracer dye 8-hydroxy-1,3,6-pyrenesulphonic acid (PTS). The percent contribution of bypass flow to root water uptake increased in response to salt stress and during the night and amounted to up to 4.4%. Bypass flow across the root cylinder of Na+ and Cl- made up 2%-12% of the net delivery of these ions to the shoot; this percentage changed little (wheat) or decreased (barley) during the night. Changes in the contribution of bypass flow to the net uptake of water, Na+ and Cl- in response to salt stress and day/night are the combined result of changes in xylem tension, the contribution of alternative cell-to-cell flow path and the requirement to generate xylem osmotic pressure.

Does night-time transpiration provide any benefit to wheat (Triticum aestivum L.) plants which are exposed to salt stress?

The study aimed to test whether night-time transpiration provides any potential benefit to wheat plants which are subjected to salt stress. Hydroponically grown wheat plants were grown at four levels of salt stress (50, 100, 150, and 200 mM NaCl) for 5-8 days prior to harvest (day 14-18). Salt stress caused large decreases in transpiration and leaf elongation rates during day and night. The quantitative relation between the diurnal use of water for transpiration and leaf growth was comparatively little affected by salt. Night-time transpirational water loss occurred predominantly through stomata in support of respiration. Diurnal gas exchange and leaf growth were functionally linked to each other through the provision of resources (carbon, energy) and an increase in leaf surface area. Diurnal rates of water use associated with leaf cell expansive growth were highly correlated with the water potential of the xylem, which was dominated by the tension component. The tissue-specific expression level of nine candidate aquaporin genes in elongating and mature leaf tissue was little affected by salt stress or day/night changes. Growing plants under conditions of reduced night-time transpirational water loss by increasing the relative humidity (RH) during the night to 95% had little effect on the growth response to salt stress, nor was the accumulation of Na+ and Cl- in shoot tissue altered. We conclude that night-time gas exchange supports the growth in leaf area over a 24 h day/night period. Night-time transpirational water loss neither decreases nor increases the tolerance to salt stress in wheat.

Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial.

BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

Unraveling the therapeutic potential of carbamoyl phosphate synthetase 1 (CPS1) in human diseases.

CPS1, the rate-limiting enzyme that controls the first reaction of the urea cycle, is responsible for converting toxic ammonia into non-toxic urea in mammals. While disruption of the functions of CPS1 leads to elevated ammonia and nerve damage in the body, mainly manifested as urea cycle disorder. Moreover, accumulating evidence has recently revealed that CPS1 is involved in a variety of human diseases, including CPS1D, cardiovascular disease, cancers, and others. In particular, CPS1 expression varies among cancers, being overexpressed in some cancers and downregulated in others, suggesting that CPS1 may be a promising cancer therapeutic target. In addition, some small-molecule inhibitors of CPS1 have been reported, which have not been confirmed experimentally in malignancies, meaning their future role is far from certain. In this review, we describe the structure and function of CPS1, highlight its important roles in various human diseases, and further discuss the potential diagnostic and therapeutic implications of small molecule compounds targeting CPS1.

Characterization of Duodenal Microbiota in Patients with Acute Pancreatitis and Healthy Controls.

OBJECTIVE: The small intestinal bacterial overgrowth (SIBO) in acute pancreatitis correlates with the severity of the disease. However, corresponding studies on the microbial composition of the duodenal mucosa of patients are uncommon. METHODS: Duodenal mucosal biopsies were collected by gastroscopy from 16 patients with mild acute pancreatitis (the Ap group) and 16 healthy individuals (the control group) and subjected to histological studies as well as bacterial 16S rRNA gene sequencing. Caerulein and L-arginine were used to induce mild acute pancreatitis (MAP) and severe acute pancreatitis (SAP) in mice, respectively, and their pancreas and duodenum were collected for histological studies. RESULTS: H&E analysis displayed no significant pathological damage in the descending duodenum of patients with acute pancreatitis compared with that of the controls. Immunofluorescence and Real-time PCR revealed that the expressions of tight junction proteins (TJPs) in duodenal mucosa were decreased in acute pancreatitis. The results of the alpha diversity analysis revealed no significant difference between the two groups, while LEfSe and the random forest revealed a few differences, indicating that the descending duodenum mucosal microbiota changed slightly in patients with mild acute pancreatitis. We observed the pathological changes and the expression of TJPs in the duodenum in the three groups of mice and found that SAP mice had more severe pathological damage in the duodenum. Furthermore, the expression of TJPs in the duodenum was lower in the MAP and SAP groups of mice compared to control mice, but it was similar in both groups. CONCLUSION: Patients with mild acute pancreatitis had mild duodenal barrier dysfunction and slight changes in duodenal mucosal microbiota.