Acupuncture for the treatment of diabetic peripheral neuropathy in the elderly: a systematic review and meta-analysis.

Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus, often causing pain or numbness in the patient's limbs and even leading to amputation and death. Elderly patients with DPN usually have higher morbidity and more severe results. Acupuncture has been widely used as an effective treatment for DPN in China. However, the efficacy of acupuncture in the treatment of DPN remains unclear. In this review, we aimed to explore the impact of acupuncture in alleviating symptoms of DPN. Method and analysis: Six databases were searched from inception to October 2023. We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and three Chinese databases, namely China National Knowledge Infrastructure (CNKI), SinoMed, and Wanfang. All randomized controlled trials related to the effect of acupuncture on DPN will be included. There was no restriction in language or publication year. The primary outcome is the response rate. The secondary outcomes are the Toronto clinical scoring system (TCSS), nerve conduction velocities (NCVs), and blood glucose before and after the treatment. Two researchers will be responsible for the selection of study, data extraction, and assessment of study quality independently. RevMan V5.1.0 software will be used to assess the risk of bias and generate data. Results: We searched 4518 studies, among which 9 RCTs were considered eligible. Overall, acupuncture treatment had a higher response rate than controls (relative risk (RR), -2.87 [95% confidence interval (CI), -5.27 to -0.48], p = 0.02) and significantly alleviated the symptoms of DPN patients, reduced their blood glucose levels, and improved their NCVs compared to the control group. This study will provide a high-quality synthesis of current available evidence for the clinical treatment of DPN with this therapy. Conclusion: The results suggested that acupuncture might be effective in improving symptoms of DPN in elderly patients. Owing to the overall low quality of the literature included, we need more large-sample, high-quality, and low-bias studies to prove it.

Prospective cohort study evaluating efficacy and safety of efgartigimod in Chinese generalized myasthenia gravis patients.

Background: Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). Methods: This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod's therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Results: Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. Discussion: A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.

Characterization of the MicroRNA profile in rheumatoid arthritis plasma exosomes and their roles in B-cell responses.

OBJECTIVE: This study aimed to identify differentially expressed microRNAs (miRNAs) in exosomes derived from the blood plasma of Rheumatoid Arthritis (RA) patients and explore their clinical significance and biological roles. METHODS: Illumina high-throughput sequencing was employed to measure miRNA expression levels in plasma exosomes, followed by validation using qRT-PCR. The correlation between exosomal miRNAs and disease activity was systematically analyzed. Additionally, the pathogenic effects of RA exosomes were investigated through bioinformatics analysis and in vitro experiments. RESULTS: Significantly reduced levels of exosomal miR-144-3p and miR-30b-5p were observed in RA patients, which were negatively correlated with DAS28 scores and anti-CCP antibody levels. ROC curve analysis showed that miR-144-3p and miR-30b-5p in plasma exosomes could effectively distinguish RA patients from healthy controls, with AUC values of 0.725 and 0.773, respectively. Combining bioinformatics analysis and in vitro experiments, it was demonstrated that plasma exosomes contribute to ongoing autoantibody production in RA by promoting B-cell differentiation and antibody production. CONCLUSION: The present study indicates that plasma exosomes from RA patients may be potentially pathogenic. Exosomal miR-144-3p and miR-30b-5p exhibit significant decreases in RA patients and are associated with disease activity, suggesting their potential as valuable biomarkers for RA.

Effects of N levels on land productivity and N2O emissions in maize-soybean relay intercropping.

BACKGROUND: Relay intercropping of maize and soybean can improve land productivity. However, the mechanism behind N2O emissions in this practice remains unclear. A two-factor randomized block field trial was conducted to reveal the mechanism of N2O emissions in a full additive maize-soybean relay intercropping. Factor A was three cropping systems - that is, monoculture maize (Zea mays L.), monoculture soybean (Glycine max L. Merr.) and maize-soybean relay intercropping. Factor B was different N supply, containing no N, reduced N and conventional N. Differences in N2O emissions, soil properties, rhizosphere bacterial communities and yield advantage were evaluated. RESULTS: The land equivalent ratio was 1.55-2.44, and the cumulative N2O emission ( C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ ) was notably lower by 60.2% in intercropping than in monoculture, respectively. Reduced N declined C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ without penalty on the yield advantages. The relay intercropping shifted soil properties - for example, soil organic matter, total N, NH 4 + $$ {\mathrm{NH}}_4^{+} $$ and protease activity - and improved the soil microorganism community - for example, Proteobacteria and Acidobacteria. Intercropping reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by directly suppressing nirS- and amoA-regulated N2O generation during soil N cycling, or nirS- and amoA-mediated soil properties shifted to reduce C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ indirectly. Reduced N directly reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by decreasing soil N content and reducing soil microorganism activities to alleviate N2O produced in soil N cycling. CONCLUSION: Conducting a full additive maize-soybean relay intercropping with reduced nitrogen supply provides a way to alleviate N2O emissions without the penalty on the yield advantage by changing rhizosphere bacterial communities and soil N cycling. © 2024 Society of Chemical Industry.

Ligand-Receptor Interaction-Induced Intracellular Phase Separation: A Global Disruption Strategy for Resistance-Free Lethality of Pathogenic Bacteria.

Addressing the global challenge of bacterial resistance demands innovative approaches, among which multitargeting is a widely used strategy. Current strategies of multitargeting, typically achieved through drug combinations or single agents inherently aiming at multiple targets, face challenges such as stringent pharmacokinetic and pharmacodynamic requirements and cytotoxicity concerns. In this report, we propose a bacterial-specific global disruption approach as a vastly expanded multitargeting strategy that effectively disrupts bacterial subcellular organization. This effect is achieved through a pioneering chemical design of ligand-receptor interaction-induced aggregation of small molecules, i.e., DNA-induced aggregation of a diarginine peptidomimetic within bacterial cells. These intracellular aggregates display affinity toward various proteins and thus substantially interfere with essential bacterial functions and rupture bacterial cell membranes in an "inside-out" manner, leading to robust antibacterial activities and suppression of drug resistance. Additionally, biochemical analysis of macromolecule binding affinity, cytoplasmic localization patterns, and bacterial stress responses suggests that this bacterial-specific intracellular aggregation mechanism is fundamentally different from nonselective classic DNA or membrane binding mechanisms. These mechanistic distinctions, along with the peptidomimetic's selective permeation of bacterial membranes, contribute to its favorable biocompatibility and pharmacokinetic properties, enabling its in vivo antimicrobial efficacy in several animal models, including mice-based superficial wound models, subcutaneous abscess models, and septicemia infection models. These results highlight the great promise of ligand-receptor interaction-induced intracellular aggregation in achieving a globally disruptive multitargeting effect, thereby offering potential applications in the treatment of malignant cells, including pathogens, tumor cells, and infected tissues.

Medcheck: a novel software for automated de-formulation of traditional Chinese medicine (TCM) prescriptions by liquid chromatography-mass spectrometry.

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Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.

Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.

Synthesis of P, N-dopped carbon nanosheets for highly sensitive fluorescence analysis of nitrofuran antibiotics in fish.

The misuse of antibiotics has caused serious impacts on food safety and human health, making it crucial to develop rapidly and highly sensitive methods for detecting trace nitrofuran antibiotics (NFs). In this study, phosphorus, nitride-doped carbon nanosheets (PN/CNs) were synthesized using a simple hydrothermal method based on graphitic carbon nitride. This prepared material showed excellent water solubility and stable optical properties. A new fluorescence sensing platform based on PN/CNs was constructed for the highly sensitive detection of four NFs. This sensitivity was mainly attributed to the fluorescence resonance energy transfer (FRET) mechanism. The limits of detection for nitrofurazone, nitrofurantoin, furazolidone and furaltadone were determined to be 13.41, 15.24, 16.37 and 19.94 nM, respectively. The high sensitivity and selectivity of PN/CNs for these four NFs were thoroughly evaluated by the Stern-Volmer equation and FRET quenching efficiency. This proposed method exhibited high sensitivity and can be successfully applied to detect NFs in fish.

Construction of Ferric-Oxide-Doped Nickel-Iron Hydroxide Electrocatalysts by Magnetic-Field-Assisted Chemical Corrosion toward Boosted Oxygen Evolution Reaction.

Transition-metal-based oxygen evolution reaction (OER) catalysts have attracted widespread attention due to their inexpensive prices, unique layered structures, and rich active sites. Currently, designing low-cost, sustainable, and simple synthesis methods is essential for the application of transition-metal-based catalysts. Here, magnetic field (MF)-assisted chemical corrosion, as a novel technology, is adopted to construct superior OER electrocatalysts. The produced Ni(Fe)(OH)2-Fe2O3 electrode exhibits an overpotential of 272 mV at a current density of 100 mA cm-2, presenting a 64 mV reduction compared to the electrode without an MF. The experimental results indicate that an MF can induce the directional growth of Fe2O3 rods and reduce their accumulation. In addition, an external MF is beneficial for the lattice dislocation of the obtained catalysts, which can increase the surface free energy, thus reducing the activation energy and accelerating the electrochemical reaction kinetics. This work effectively combines a magnetic field with chemical corrosion and electrochemical energy, which offers a novel strategy for the large-scale development of environmentally friendly and superior electrocatalysts.

Fabrication of a magnetic functionalized chitosan hydrogel for effective extraction of aflatoxins from cereals.

A magnetic adsorbent was synthesized by coupling magnetic nanoparticles, UiO-66-NH2 and 1-butyl-trimethylimidazole bromide ([BMIM][Br]) to chitosan (CS)-based composite conveniently. A series of modern characterizations were employed to assess its properties. The results showed that UiO-66-NH2 was uniformly distributed within the composite via in-situ growth, which can enhance the porosity obviously. The introduction of various ligands enables the composite to exhibit excellent extraction performance for four aflatoxins (AFs) through multiple interactions. The adsorption mechanism was elucidated and the main factors affecting extraction efficiency were evaluated. Under optimal conditions, the limits of detection (LODs) ranged from 0.08 to 0.56 µg/kg. The established method was successfully utilized to determine AFs from cereal samples (rice, glutinous rice, wheat, soybean, paddy, and corn) with satisfactory recovery of 77% âˆ¼ 119% with relative standard deviations (RSDs) of 1.0% âˆ¼ 11.7% (n = 5). The adsorbent demonstrated sufficient robustness for repeated use at least six times without obvious damage of extraction property.

A multimodal physiological and psychological dataset for human with mental stress induced myocardial ischemia.

Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored treatment strategies, yet public data scarcity hampers understanding. Given the higher incidence of both conditions in women, this study prospectively enrolled 80 female ANOCA and 39 age-matched female controls, subjecting them to three types of mental stress tasks. ECGs were continuously monitored across Rest, Stress, and Recover stages of the mental stress tasks, with PET/CT imaging during the Stress stage to evaluate myocardial perfusion. With PET/CT serving as the gold standard for MSIMI diagnosis, 35 of the 80 ANOCA patients were diagnosed as MSIMI. Using ECG variables from different stages of mental stress tasks, we developed five machine learning models to diagnose MSIMI. The results showed that ECG data from different stages provide valuable information for MSIMI classification. Additionally, the dataset encompassed demographic details, physiological, and blood sample test results of the patients. We anticipate this new dataset will significantly push further progress in ANOCA and MSIMI research.

DNA tetrahedral scaffold-corbelled self-feedback circuit for dual-mode ratiometric biosensing with Ru@COF-LZU1 accelerator.

Sensitive, reliable, and specific detection of microRNAs (miRNAs) is a key objective for disease diagnosis and prognosis. Here, a ratiometric fluorescent/electrochemiluminescent (FL/ECL) sensor was designed for the dual-mode detection of miRNA-122, a hepatocellular carcinoma biomarker. The strong ECL emission was achieved from imine-linked covalent organic framework (COF-LZU1) accelerator enriched Ru(bpy)32+ molecules (Ru@COF-LZU1), which was applied as a delimited reaction micro-reactor to enhance ECL emission. Impressively, to construct an efficient sensing platform, self-feedback circuit was grafted at the vertex of DNA tetrahedral scaffold (DTS), which could provide a solution-phase-like environment and transform miRNA-122 into abundant single-stranded DNAs on the disposable electrode. Simultaneously, the carboxyfluorescein (FAM) tagged DNA segment was cleaved and released into the reaction solution, bringing in the recovery of FL response (FL on). Finally, the introduction of glucose oxidase (GOD) could generate H2O2 by in situ catalyzing GOD to glucose, resulting in the decrease of ECL signal (ECL off). Relying on FL/ECL ratio value, miRNA-122 was quantified with high sensitivity, well selectivity, stability and favorable practicability, suggesting that the proposed biosensor hold great potential for clinical diagnosis.

Millennial changes and cooling trends in land surface warm-season temperatures during the Holocene.

The scarcity of proxies and calibration models for quantitatively reconstructing millennial timescale seasonal temperature tremendously constraints our understanding of the Holocene thermal variation and its driven mechanisms. Here, we established two global warm-season temperature models by applying deep learning neural network analysis to the branched tetraether membrane lipids originating from surface soil and lacustrine sediment bacteria. We utilized these optimal models in global well-dated lacustrine, peatland, and loess profiles covering the Holocene. All reconstructions of warm-season temperatures, consistent with climate model simulations, indicate cooling trends since the early Holocene, primarily induced by decreased solar radiation in the Northern Hemisphere due to the precession peak at the early. We further demonstrated that the membrane lipids can effectively enhance the future millennial seasonal temperature research, including winter temperatures, without being restricted by geographical location and sedimentary carrier.

Functional roles and engineering strategies to improve the industrial functionalities of lactic acid bacteria during food fermentation.

In order to improve the flavor profiles, food security, probiotic effects and shorten the fermentation period of traditional fermented foods, lactic acid bacteria (LAB) were often considered as the ideal candidate to participate in the fermentation process. In general, LAB strains possessed the ability to develop flavor compounds via carbohydrate metabolism, protein hydrolysis and amino acid metabolism, lipid hydrolysis and fatty acid metabolism. Based on the functional properties to inhibit spoilage microbes, foodborne pathogens and fungi, those species could improve the safety properties and prolong the shelf life of fermented products. Meanwhile, influence of LAB on texture and functionality of fermented food were also involved in this review. As for the adverse effect carried by environmental challenges during fermentation process, engineering strategies based on exogenous addition, cross protection, and metabolic engineering to improve the robustness and of LAB were also discussed in this review. Besides, this review also summarized the potential strategies including microbial co-culture and metabolic engineering for improvement of fermentation performance in LAB strains. The authors hope this review could contribute to provide an understanding and insight into improving the industrial functionalities of LAB.

Effect of Pressure and Nonpressure Dressings on Postoperative Complications in Patients With Mixed Hemorrhoids: A Single-blind Controlled Study.

PURPOSE: To compare the clinical effects of nonpressure and pressure dressings on the postoperative complications of modified Milligan-Morgan hemorrhoidectomy. DESIGN: Randomized controlled trial. METHODS: A total of 186 patients with grade II to III mixed hemorrhoids who had been excluded from cardiovascular and cerebrovascular diseases and anorectal surgery were included and randomly assigned to the nonpressure dressings group and the pressure dressings group by random number table. The incidence of acute urinary retention and medical adhesive-related skin injury, pain, hemostatic effect, anal distension, anal edema, use of analgesics, length of hospital stay, and hospitalization costs were compared between the two groups. The Consolidated Standards of Reporting Trials checklist for randomized controlled trials was used in this study. FINDINGS: The incidence of acute urinary retention in both men and women was significantly lower in the nonpressure dressing group (relative risk [RR] = 0.20, 95% confidence interval [CI] [0.13, 0.37], P = .002); (RR = 0.47, 95% CI [0.22, 0.76], P = .015). The postoperative pain at 6 hours/18 hours/25 hours was significantly lower in the nonpressure dressing group (P < .001, P = .004 < 0.05, P = .009). The anal distension at 6 hours and the number of patients who used analgesics were significantly lower in the nonpressure dressing group (P < .001). The incidence of medical adhesive-related skin injuries was significantly lower in the nonpressure dressing group (RR = 0.061, 95% CI [0.020, 0.189], P < .001). No primary bleeding was observed in both groups. However, there were no significant differences between both groups in terms of anal edema scores, length of stay, or hospitalization expenses. No adverse events were reported in either group during the study period. CONCLUSIONS: Nonpressure dressings can effectively reduce the incidence of acute urinary retention and medical adhesion-related skin injury after surgery for grade III to IV mixed hemorrhoids. They can also safely relieve pain and distension.

Nonadiabatic Coupling-Induced Quantum Coherence in Two-Dimensional Materials.

Two-dimensional materials provide a rich platform demonstrating quantum effects, and the process of electron-hole recombination occurring in them has significant applications in the fields of the photocatalytic and optoelectronic community. Here, we present nonadiabatic coupling-induced quantum coherence and quantum beats in Al-doped blue phosphorene. The work improves our understanding and utilization of nonadiabatic coupling in low-dimensional materials from a new perspective. In addition, our investigations provide meaningful guidance for manipulating quantum coherence in low-dimensional materials and promoting their novel optoelectronic properties.

Bio-accumulation and health risk assessments of per- and polyfluoroalkyl substances in wheat grains.

Per- and polyfluoroalkyl substances (PFASs) have been widely detected in various food, which has attracted worldwide concern. However, the factors influencing the transfer and bio-accumulation of PFASs from soils to wheat in normal farmland, is still ambiguous. We investigated the PFASs accumulation in agricultural soils and grains from 10 cites, China, and evaluated the health risks of PFASs via wheat consumption. Our results show that ∑PFASs in soils range from 0.34 µg/kg to 1.59 µg/kg with PFOA and PFOS dominating, whilst ∑PFASs in wheats range from 2.74 to 6.01 µg/kg with PFOA, PFBA and PFHxS dominating. The lower pH conditions and high total organic carbon (TOC) could result in the higher accumulation of PFASs in soils and subsequently in wheat grains, whilst the bioaccumulation factors of PFASs increase with increasing pH conditions but not with TOC. The estimated daily intake (EDI) values of PFBA, PFOA, and PFHxS are relatively high, but data supports that ingesting wheat grains does not result in any potential risk to the human beings. Our studies provided more information about PFASs accumulation in wheat grains, and help us understand the current potential risks of PFASs in food.

TMC6 functions as a GPCR-like receptor to sense noxious heat via Gαq signaling.

Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser780 to Pro810. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca2+ release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat.

Biosynthesis of GMGT lipids by a radical SAM enzyme associated with anaerobic archaea and oxygen-deficient environments.

Archaea possess characteristic membrane-spanning lipids that are thought to contribute to the adaptation to extreme environments. However, the biosynthesis of these lipids is poorly understood. Here, we identify a radical S-adenosyl-L-methionine (SAM) enzyme that synthesizes glycerol monoalkyl glycerol tetraethers (GMGTs). The enzyme, which we name GMGT synthase (Gms), catalyzes the formation of a C(sp3)-C(sp3) linkage between the two isoprenoid chains of glycerol dialkyl glycerol tetraethers (GDGTs). This conclusion is supported by heterologous expression of gene gms from a GMGT-producing species in a methanogen, as well as demonstration of in vitro activity using purified Gms enzyme. Additionally, we show that genes encoding putative Gms homologs are present in obligate anaerobic archaea and in metagenomes obtained from oxygen-deficient environments, and appear to be absent in metagenomes from oxic settings.