Symbiont-mediated antisense RNA delivery controls Nosema ceranae infections in Apis mellifera.

Nosema ceranae is a main parasite for honeybees (Apis mellifera) which causes colony collapse in spring. Effective management of N. ceranae infections in bees is imperative for beekeepers. RNA interference (RNAi) has been proven a promising method to control bee pathogens, including IAPV, Varroa destructor, and Nosema. Most studies in this field focused on oral inoculation of double-stranded RNA (dsRNA). We developed an easier method with long-term RNAi effects by engineering the bee symbiont, Bacillus subtilis, to deliver single-stranded antisense RNA (asRNA) in the bee guts, targeting N. ceranae genes. We interfered with the expression of a spore wall protein (SWP12) and a polar tube protein (PTP3) of N. ceranae, resulting in a 60.5% increase in bee lifespan and a 72.7% decrease in Nosema spore load. Our research introduced a novel approach to bee parasite control: B. subtilis-mediated asRNA delivery. Our strategy simplifies the procedure of RNAi, presenting a more efficient mechanism with both prophylactic and therapeutic effects on N. ceranae-infected bees.

A novel triple-signal biosensor based on ZrFe-MOF@PtNPs for ultrasensitive aflatoxins detection.

The development of more sensitive, stable, and portable biosensors is crucial for meeting the growing demands of diverse and complex detection environments. MOF-based nanozymes have emerged as excellent optical reporters, making them ideal signal donors for constructing multi-signal lateral flow immunoassays (LFIA). In this study, a ZrFe-MOF@PtNPs nanocomposite was synthesized by uniformly depositing platinum nanoparticles (PtNPs) onto the surface of ZrFe-MOFs using an impregnation-reduction method. The ZrFe-MOF@PtNPs exhibited broad absorption spectra, excellent peroxidase-like activity (SA = 21.77 U/mg), high solvent stability, and efficient antibody binding capability. A portable LFIA platform was developed based on ZrFe-MOF@PtNPs and a smartphone for the targeted detection of carcinogenic aflatoxins. This method enabled the readout of colorimetric, fluorescent, and catalytic signals, significantly enhancing detection sensitivity, ensuring result accuracy, and expanding the dynamic detection range. For aflatoxin M1, the calculation of the detection limit of the three signal modes reached as low as 0.0062 ng/mL, which is two orders of magnitude more sensitive than AuNPs-LFIA (0.1839 ng/mL). This study provides effective guidance for multifunctional modification of MOFs and serves as a reference for the application of MOF-based nanozymes in point-of-care biosensors.

Dual-functional probe-based multi-signal immunosensor platform for tropane alkaloids: Verification and evaluation.

This study aims to realise rapid detecting of tropane alkaloids (TAs) in food. For this purpose, a broad-spectrum single-chain fragment variable was fused with horseradish peroxidase to create an antibody-enzyme complex (AEC) with antigen recognition and catalytic activity. A multi-signal immunosensor platform based on AEC in the direct competitive reaction mode was constructed using 3,3',5,5'-tetramethylbenzidine and 10-acetyl-3,7-dihydroxyphenoxazine as substrates. The sensitivity of TAs in the immunosensor platform ranged from 0.25 µg/kg to 7912.46 µg/kg. Honey was selected as a representative food sample, and the limit of detection of TAs in honey ranged from 0.02 µg/kg to 409.11 µg/kg, with a recovery rate of 65.7 %-117.1 % and a coefficient of variation less than 21.4 %. Results showed that the immunosensor platform possesses satisfactory accuracy and precision, which highlights its potential for practical applications and its suitability as an ideal tool for rapid screening of TAs in food.

Hyper-Interferon Sensitive influenza induces adaptive immune responses and overcomes resistance to anti-PD-1 in murine non-small cell lung cancer.

Despite recent advances in immunotherapy with immune checkpoint inhibitors (ICI), many patients with non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) with engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment (TME) and augment anti-tumor T cell responses to overcome immune resistance. We engineered a live attenuated viral vaccine, Hyper-Interferon Sensitive virus (HIS), by conducting a genome-wide functional screening and introducing eight interferon (IFN)-sensitive mutations in the influenza genome. Compared to wild-type (WT) influenza, HIS replication was attenuated in immunocompetent hosts, enhancing its potential as a safe option for cancer therapy. HIS ISV elicited robust yet transient type I IFN responses in murine NSCLCs, leading to an enrichment of polyfunctional effector Th1 CD4 and cytotoxic CD8 T cells into the tumor. HIS ISV demonstrated enhanced anti-tumor efficacy compared to WT in multiple syngeneic murine models of NSCLC with distinct driver mutations and varying mutational burden. This efficacy was dependent on host type 1 IFN responses and T lymphocytes. HIS ISV overcame resistance to anti-PD-1 in LKB-1 deficient murine NSCLC, resulting in improved overall survival and enduring systemic tumor-specific immunity. These studies provide compelling evidence to support further clinical evaluation of HIS as a novel 'off-the-shelf' ISV strategy for patients with NSCLC refractory to ICI.

Evidence and potential mechanism of action of indigo naturalis and its active components in the treatment of psoriasis.

BACKGROUND: Indigo naturalis is effective against psoriasis. Indigo, indirubin and tryptanthrin, the main active components of indigo naturalis, have anti-inflammatory properties. OBJECTIVE: To evaluate the efficacy and safety of indigo naturalis and its active components in the treatment of psoriasis. METHODS: Seven databases were searched for studies of indigo naturalis and its active components for the treatment of psoriasis. RESULTS: The findings demonstrated a higher response rate in the Chinese herbal medicine (CHM) formula groups than in the control group for Psoriasis Area and Severity Index 60 (PASI60) (Rate difference [RD] = 0.22, p < .0001). Among all adverse events, only the incidence of gastrointestinal adverse reactions was higher in the CHM formula group than in the control group (RD = 0.09, p < .0001). In preclinical in vivo studies, indirubin showed better performance in improving the phenotype of psoriasis-like mice compared to that in controls, including the PASI score (mean difference [MD] = -3.58, p < .0001), epidermal thickness (MD = -29.13, p < .0001), interleukin-(IL) 17 A mRNA expression (MD = -2.27, p = .0066) and IL-23 mRNA (MD = -5.36, p = .01). CONCLUSION: Indigo naturalis combined with conventional treatments is useful for treating psoriasis. Indigo naturalis display anti-proliferative, anti-inflammatory and anti-angiogenic effects by regulating the TAK1, JAK3/STAT3, Wnt/ß-catenin, Akt/PKB, FAK and AP-1/c-Jun pathway.

Indigo naturalis, a Chinese herb and its main active components, indigo, indirubin and tryptanthrin are effective in treating psoriasis.Indigo naturalis, indirubin, indigo and tryptanthrin have anti-proliferative, anti-inflammatory and anti-angiogenic effects via regulating the TAK1, JAK3/STAT3, Wnt/ß-catenin, Akt/PKB, FAK and AP-1/c-Jun pathways.

Toward Onboard Proportional Control of Multi-Chamber Soft Pneumatic Robots: A Magnetorheological Elastomer Valve Array.

Soft pneumatic actuators (SPAs) are commonly used in various applications because of their structural compliance, low cost, ease of manufacture, high adaptability, and safe human-robot interaction. The traditional approach for achieving proportional control of soft pneumatic robots requires the use of industrial proportional valves or syringe drivers, which are not only rigid and bulky but also hard to be integrated into the body of soft robots. In our previous research, we developed a Magnetorheological elastomer (MRE)-based soft valve that showed advantages for controlling SPAs due to its compliance, compactness, robustness, and compatibility for continuous pressure modulation. Modern soft robots with multiple chambers require more MRE valves onboard for their control. However, merely packing more MRE valves for soft robots can cause problems like magnetic interference, flow rate deviation, and overheating. Therefore, in this study, we proposed a two-dimensional MRE valve array design to solve issues of magnetic interference and overheating when expanding from a single MRE proportional valve into an integrated array. The magnetic interference and the overheating problem were investigated through multiphysics simulation, bringing the optimal choice of valve spacing (1.2 times the single valve diameter), magnetic coil pole arrangement (same pole), and the cooling system design (internal cooling chamber with flowing water). Physical experiments showed that our MRE valve array maintained its original flowrate performance with low magnetic interference (0.89 mT) and low coil temperature (under 73.9°C for 5 min).

Berberine attenuates 5-fluorouracil-induced intestinal mucosal injury by modulating the gut microbiota without compromising its anti-tumor efficacy.

Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1ß), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Insight of Chinese Herbal Medicine in Treating Osteoporosis: Achievements from 2013 to 2023.

Osteoporosis is the most common bone metabolic disease, and it is becoming increasingly common as the global population ages. Osteoporosis and its complications, such as fractures and pain, negatively affect patient quality of life and easily lead to disability, placing enormous burdens on society. Although several anti-osteoporosis drugs are currently available, many adverse reactions have been observed during the long-term application of these drugs. Therefore, safer and more useful medications are urgently needed to replace those currently available. Chinese herbal medicine has been extensively used to treat osteoporosis, and the current literature confirms that such medicines have anti-osteoporosis effects, are safe, and have minimal side effects. Thus, Chinese herbal medicines are natural alternatives to pharmaceutical approaches to treating osteoporosis, and these medicines must be further developed and utilized. In this article, we review the mechanisms underlying the anti-osteoporosis effects of single herbal extracts and traditional Chinese medicine (TCM) formulas that have been elucidated since 2013, providing key evidence and support for future research on the anti-osteoporosis effects of Chinese herbal medicines. In addition, due to the complexity of the ingredients in Chinese herbal medicine, more thorough investigations are needed to determine the specific ingredients that are effective in osteoporosis treatment. Therefore, identifying the effective ingredients of Chinese herbal medicines will be a necessary focus in laboratory research and clinical application.

Doubling Power Conversion Efficiency of Si Solar Cells.

Improving solar cells' power conversion efficiency (PCE) is crucial to further the deployment of renewable electricity. In addition, solar cells cannot function at exceedingly low temperatures owing to the carrier freeze-out phenomenon. This report demonstrates that through temperature regulation, the PCE of monocrystalline single-junction silicon solar cells can be doubled to 50-60% under monochromatic lasers and the full spectrum of AM 1.5 light at low temperatures of 30-50 K by inhibiting the lattice atoms' thermal oscillations for suppressing thermal loss, an inherent feature of monocrystalline Si cells. Moreover, the light penetration, determined by its wavelength, plays a critical role in alleviating the carrier freeze-out effect and broadening the operational temperature range of silicon cells to temperatures as low as 10 K. Understanding these new observations opens tremendous opportunities for designing solar cells with even higher PCE to provide efficient and powerful energy sources for cryogenic devices and outer and deep space explorations.

Risk factors and prognostic analysis of right ventricular dysfunction after lung resection for NSCLC.

Objectives: Lung cancer is the leading cause of cancer death, and 80-85% of all lung cancer cases are non-small cell lung cancer (NSCLC). Surgical resection is the standard treatment for early-stage NSCLC. However, lung resection, a surgical procedure, can result in complications and increased mortality. Recent studies have shown a significant correlation between complications after lung resection and right ventricular dysfunction. Methods: Transthoracic echocardiography-derived right ventricular-pulmonary artery coupling (RV-PAC) was utilized to assess right ventricular function in these patients. Multivariate logistic regression analysis was also conducted to assess risk factors independently associated with RV-PA uncoupling. The 3- and 5-year cumulative survival rates were estimated with Kaplan-Meier curves, and differences between groups were analyzed using the Mantel-Cox log-rank test. Results: RV-PA uncoupling was defined as a TAPSE/PASP value < 0.67 mm/mm Hg according to spline analysis. The results of multivariable logistic regression analysis indicated that diabetes is an independent risk factor for right ventricular dysfunction after lung resection in patients with NSCLC. Kaplan-Meier analysis revealed a significant decrease in the survival rate of patients with RV-PA uncoupling at both the 3-year follow-up (73% vs 40%, p < 0.001) and 5-year follow-up (64% vs 37%, p < 0.001). Conclusions: After lung resection for NSCLC, the patient's right ventricular function predicts prognosis. Patients with right ventricular dysfunction, particularly those with diabetes mellitus, have a worse prognosis. It is crucial to actively prevent and correct risk factors to reduce the mortality rate in these patients.

DHXT1, a Virulence Factor of Dactylellina haptotyla, Regulates Pathogenicity by Participating in Trap Formation and Metabolite Synthesis.

The capsule-associated protein 10 gene (CAP10) is indispensable due to its involvement in pod formation and virulence maintenance in Cryptococcus neoformans. The function of the CAP10 gene in nematode-predatory fungi remains unreported. As a typical nematode-trapping fungus, Dactylellina haptotyla efficiently captures nematodes using adhesive knobs, which has potential applications in the biological control of plant-parasitic nematodes. In this study, we investigated the function of DHXT1 (a CAP10 homologous protein) in D. haptotyla-nematode interactions based on the disruption and overexpression of DHXT1, phenotypic analysis and metabolomic analysis. As a result, it was shown that the disruption of the DHXT1 gene causes a marked decrease in the number of adhesive knobs, and on the contrary, the overexpression of the DHXT1 gene causes a substantial increase in the number of adhesive knobs. Interestingly, the variety of metabolites increased with the disruption of the DHXT1 and decreased with the overexpression of the DHXT1 gene. The results suggest that DHXT1 effects pathogenicity through its involvement in adhesive knobs' formation and metabolite synthesis and serves as a key virulence factor in D. haptotyla.

Design and synthesis of 7-membered lactam fused hydroxypyridinones as potent metal binding pharmacophores (MBPs) for inhibiting influenza virus PAN endonuclease.

Since influenza virus RNA polymerase subunit PAN is a dinuclear Mn2+ dependent endonuclease, metal-binding pharmacophores (MBPs) with Mn2+ coordination has been elucidated as a promising strategy to develop PAN inhibitors for influenza treatment. However, few attentions have been paid to the relationship between the optimal arrangement of the donor atoms in MBPs and anti-influenza A virus (IAV) efficacy. Given that, the privileged hydroxypyridinones fusing a seven-membered lactam ring with diverse side chains, chiral centers or cyclic systems were designed and synthesized. A structure-activity relationship study resulted in a hit compound 16l (IC50 = 2.868 ± 0.063 µM against IAV polymerase), the seven-membered lactam ring of which was fused a pyrrolidine ring. Further optimization of the hydrophobic binding groups on 16l afforded a lead compound (R, S)-16s, which exhibited a 64-fold more potent inhibitory activity (IC50 = 0.045 ± 0.002 µM) toward IAV polymerase. Moreover, (R, S)-16s demonstrated a potent anti-IAV efficacy (EC50 = 0.134 ± 0.093 µM) and weak cytotoxicity (CC50 = 15.35 µM), indicating the high selectivity of (R, S)-16s. Although the lead compound (R, S)-16s exhibited a little weaker activity than baloxavir, these findings illustrated the utility of a metal coordination-based strategy in generating novel MBPs with potent anti-influenza activity.

ZMYND12 serves as an IDAd subunit that is essential for sperm motility in mice.

Inner dynein arms (IDAs) are formed from a protein complex that is essential for appropriate flagellar bending and beating. IDA defects have previously been linked to the incidence of asthenozoospermia (AZS) and male infertility. The testes-enriched ZMYND12 protein is homologous with an IDA component identified in Chlamydomonas. ZMYND12 deficiency has previously been tied to infertility in males, yet the underlying mechanism remains uncertain. Here, a CRISPR/Cas9 approach was employed to generate Zmynd12 knockout (Zmynd12-/-) mice. These Zmynd12-/- mice exhibited significant male subfertility, reduced sperm motile velocity, and impaired capacitation. Through a combination of co-immunoprecipitation and mass spectrometry, ZMYND12 was found to interact with TTC29 and PRKACA. Decreases in the levels of PRKACA were evident in the sperm of these Zmynd12-/- mice, suggesting that this change may account for the observed drop in male fertility. Moreover, in a cohort of patients with AZS, one patient carrying a ZMYND12 variant was identified, expanding the known AZS-related variant spectrum. Together, these findings demonstrate that ZMYND12 is essential for flagellar beating, capacitation, and male fertility.

Natural Prenylflavonoids from Sophora flavescens Root Bark against Multidrug-Resistant Methicillin-Sensitive Staphylococcus aureus Targeting the Membrane Permeability.

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds (1-30) were isolated from the root bark of S. flavescens, consisting of 20 new compounds (1-20). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 µg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.

Iodine nutritional status and its associations with thyroid function of pregnant women and neonatal TSH.

Introduction: Iodine serves as a crucial precursor for the synthesis of thyroid hormones and plays an import role in both pregnant women and their offspring. The relationships between iodine nutritional status and maternal thyroid function and neonatal outcomes remain inconclusive in areas with adequate iodine nutrition. This study aims to investigate their correlations. Methods: Blood, morning urine and 24-hour urine were collected from the pregnant women to measure thyroid functions, serum iodine concentration (SIC), morning urine iodine concentration (UIC) and 24-hour urine iodine excretion (24-hour UIE). Indicators of their offspring's neonatal indexes were recorded. Results: A total of 559 pregnant women were enrolled in this study. The iodine indicators including Tg, 24-hour UIE and morning UIC were significantly different among the euthyroid pregnant women and those with different thyroid disorders. The levels of FT3, FT4, and SIC exhibited a gradual decline and the concentration of TSH exhibited a gradual increase trend throughout the progression of pregnancy in euthyroid pregnant women. There were no significant differences in neonatal outcomes and neonatal TSH values among euthyroid pregnant women and thyroid disorders pregnant women. SIC had a significant impact on maternal FT4 levels throughout all three trimesters, with varying degrees of importance observed in each trimester. TSH level emerged as the primary determinant of FT4 during the first trimester, while SIC exerted a predominant influence on FT4 levels in the second and third trimesters. The prevalence of thyroid disorders in pregnant women was the lowest when the SIC of pregnant women was probable in the range of 60~70 µg/L, 24-hours UIE was in the range of 250~450 µg, and Tg was in the range of 9~21 µg/L. Maternal TSH exhibited a notable influence on neonatal TSH levels, particularly at the 50th and 75th quantiles. Among the iodine nutritional indicators, SIC and morning UIC demonstrated higher AUC values for abnormal FT4 and TSH, respectively. Discussion: The iodine nutrition status of pregnant women exerts an impact on their thyroid function and prevalence of thyroid disorders, and neonatal TSH was affected by maternal TSH. SIC may be a better indicator for iodine nutritional assessment than other indexes.

MiR-23b-3p alleviates Sjögren's syndrome by targeting SOX6 and inhibiting the NF-κB signaling.

OBJECTIVE: MicroRNA-23b-3p has been demonstrated to act as a safeguard against several autoimmune diseases. However, its role in Sjögren's syndrome (SS) remains unclear. METHODS: In order to investigate its role in SS, we administered agomiR-23b-3p or agomiR-NC to non-obese diabetic (NOD) mice via tail vein weekly for 6 weeks. The study examined the saliva flow rate, histological changes in submandibular glands, and levels of autoantibodies. Additionally, the levels of several cytokines, cell apoptosis, and NF-κB signaling were evaluated. The protective effect of miR-23b-3p was confirmed in a cell model. RESULTS: The results demonstrated that miR-23b-3p overexpression improved salivary flow rates, inhibited lymphocyte infiltration, reduced cytokine levels, and suppressed cell apoptosis in NOD mice. Moreover, NF-κB signaling was inactivated following miR-23b-3p overexpression. In a cellular model of SS, overexpression of miR-23b-3p protected submandibular gland epithelial cells exposed to IFN-γ against apoptosis and inflammation by targeting SOX6. CONCLUSIONS: The study concludes that miR-23b-3p alleviates SS by targeting SOX6 and inhibiting the NF-κB signaling pathway. The miR-23b-3p/SOX6 axis represents a promising avenue for the development of novel therapeutic strategies for SS.

Label-free direct detection of melamine using functionalized gold nanoparticles-based dual-fluorescence colorimetric nanoswitch sensing platform.

Developing a simple, economical, sensitive, and selective method for label-free direct detection analytes is attractive, especially the strategies that could achieve signal amplification without complicated operations. Herein, a dual-fluorescence colorimetric nanoswitch sensing platform for label-free direct melamine (MEL) detection was established. We first explored the relationship between MEL-induced aggregation of gold nanoparticles (AuNPs) and size and determined the optimal size to be 37 nm. Using surfactant Triton X-100 to modify AuNPs and clarify possible interaction mechanisms to improve detection performance. The dynamic changes of surface plasmon resonance absorption peaks in the dispersed and aggregated states of AuNPs were skillfully utilized to match the emission of multicolor gold nanoclusters to trigger the multi-inner filter effect. Accompanied by the addition of MEL-induced AuNPs to change from dispersed to aggregated state, the fluorescence of green-emitting and red-emitting gradually turned on and turned off, respectively. The fluorescence turn-on mode detection limit was 10 times higher than the colorimetric method and as low as 5.5 ng/mL; the detection took only 10 min. The sensor detected MEL in spiked milk samples with a good recovery in the range of 81.2-111.0 % with a coefficient of variation less than 11.4 % and achieved a good correlation with commercial kits. The proposed sensor integrates numerous merits of label-free, multi-signal readout, self-calibration, simple operations, and economical, which provides a promising tool for convenient on-site detection of MEL.

Supramolecular Modifying Nafion with Fluoroalkyl­Functionalized Polyoxometalate Nanoclusters for High­Selective Proton Conduction.

Fluoroalkyl-grafted polyoxometalate nanoclusters are used as supramolecular additives to precisely modify the ionic domains of Nafion, which can increase the proton conductivity and selectivity simultaneously. The resulting hybrid membranes show significantly enhanced power density in fuel cells and improved energy efficiency in vanadium flow batteries.

Effectiveness of home-based cardiac telerehabilitation based on wearable ECG or heart rate monitoring devices in patients with heart disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices in patients with heart disease. METHODS: We searched eight electronic databases under the guidance of Cochrane Handbook and PRISMA recommendations. RESULTS: The meta-analysis included data from 14 articles (15 RCTs) representing 1314 participants. A significant improvement in left ventricular ejection fraction [MD = 2.12, 95 % CI (1.21, 3.04), P < 0.001], 6-minute walk distance [MD = 40.00, 95 % CI (21.72, 58.29), P < 0.001] and peak oxygen intake [MD = 2.24, 95 % CI (1.38, 3.10), P < 0.001] were observed in the home-based cardiac telerehabilitation group. But it had no difference in anxiety [SMD = -0.83, 95 % CI (-1.65, -0.02), P = 0.05] and depression [SMD = -0.59, 95 % CI (-1.26, 0.09), P = 0.09]. Subgroup analyses revealed that interventions of no less than 3 months improved anxiety [SMD = -1.11, 95 % CI (-2.05, -0.18), P = 0.02] and depression [SMD = -1.01, 95 % CI (-1.93, -0.08), P = 0.03]. CONCLUSION: Home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices has a positive effect on cardiac function. Long-term (≥ 3 months) cardiac rehabilitation might benefit individuals suffering from anxiety or depression.

DDAH1 promotes neurogenesis and neural repair in cerebral ischemia.

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.