The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota.

BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.

Formation and non-covalent interactions of binary and ternary complexes based on ß-casein, Lentinus edodes mycelia polysaccharide, and taxifolin.

Polyphenols, polysaccharides, and proteins are essential nutrients and functional substances present in food, and when present together these components often interact with each other to influence their structure and function. Proteins and polysaccharides are also excellent carrier materials for polyphenols. In this context, this study investigated the non-covalent interactions between taxifolin (TAX), Lentinus edodes mycelia polysaccharide (LMP), and ß-casein (ß-CN). ß-CN and LMP spontaneously formed nanocomplexes by hydrogen bonds and van der Waals forces. The quenching constant and binding constant were (1.94 ± 0.02) × 1013 L mol-1 s-1 and (3.22 ± 0.17) × 105 L mol-1 at 298 K, respectively. The altered conformation of ß-CN, resulting from the binding to LMP, affected the interaction with TAX. LMP significantly enhanced the binding affinity of TAX and ß-CN, but did not change the static quenching binding mode. The binding constant for ß-CN-TAX was (3.96 ± 0.09) × 1013 L mol-1, and that for the interaction between TAX and ß-CN-LMP was (32.06 ± 0.05) × 1013 L mol-1. In summary, ß-CN-LMP nanocomplexes have great potential as a nanocarrier for polyphenols, and this study provides a theoretical foundation for the rational design of non-covalent complexes involving LMP and ß-CN, both in binary and ternary configurations.

Neutrophil extracellular traps formation may be involved in the association of propranolol with the development of portal vein thrombosis.

BACKGROUND & AIMS: Nonselective ß blockers (NSBBs) facilitate the development of portal vein thrombosis (PVT) in liver cirrhosis. Considering the potential effect of NSBBs on neutrophils and neutrophil extracellular traps (NETs), we speculated that NSBBs might promote the development of PVT by stimulating neutrophils to release NETs. MATERIALS AND METHODS: Serum NETs biomarkers were measured, use of NSBBs was recorded, and PVT was evaluated in cirrhotic patients. Carbon tetrachloride and ferric chloride (FeCl3) were used to induce liver fibrosis and PVT in mice, respectively. After treatment with propranolol and DNase I, neutrophils in peripheral blood, colocalization and expression of NETs in PVT specimens, and NETs biomarkers in serum were measured. Ex vivo clots lysis analysis was performed and portal vein velocity and coagulation parameters were tested. RESULTS: Serum MPO-DNA level was significantly higher in cirrhotic patients treated with NSBBs, and serum H3Cit and MPO-DNA levels were significantly higher in those with PVT. In fibrotic mice, following treatment with propranolol, DNase I significantly shortened the time of FeCl3-induced PVT formation, lowered the peripheral blood neutrophils labelled by CD11b/Ly6G, inhibited the positive staining of H3Cit and the expression of H3Cit and MPO proteins in PVT tissues, and reduced serum nucleosome level. Furthermore, the addition of DNase I to tissue plasminogen activator (tPA) significantly accelerated clots lysis as compared with tPA alone. Propranolol reduced portal vein velocity in fibrotic mice, but did not influence coagulation parameters. CONCLUSION: Our study provides a clue to the potential impact of NETs formation on the association of NSBBs with the development of PVT.

Effects of probiotic supplementation on 12 min run performance, mood management, body composition and gut microbiota in amateur marathon runners: A double-blind controlled trial.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Acidic Environment-Responsive Metal Organic Framework-Mediated Dihydroartemisinin Delivery for Triggering Production of Reactive Oxygen Species in Drug-Resistant Lung Cancer.

Background: Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics has been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy and leading to notable side effects during the treatment. Purpose: We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable and targeted DHA release properties, leading to enhanced antitumor effects while reducing potential side effects. Methods: D-ZIF was prepared by one-pot synthesis method using methylimidazole (MIM), Zn(NO3)2•6H2O and DHA. We characterized the physical and chemical properties of D-ZIF by TEM, DLS, XRD, FT-IR, and TG. We measured the drug loading efficiency and the cumulative release of DHA in different pH conditions. We evaluated the cytotoxicity of D-ZIF on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) cells by CCK8 in vitro. We explored the possible antitumor mechanism of D-ZIF by Western blot. We evaluated the biocompatibility and hemolysis of D-ZIF and explored the in vivo antitumor efficiency in mice model by TUNEL testing and blood biomarker evaluations. Results: D-ZIF showed rhombic dodecahedral morphology with size of 129±7.2 nm and possessed a noticeable DHA encapsulation efficiency (72.9%). After 48 hours, D-ZIF released a cumulative 70.0% of the loaded DHA at pH 6.5, and only 42.1% at pH 7.4. The pH-triggered programmed release behavior of D-ZIF could enhance anticancer effect of DHA while minimizing side effects under normal physiological conditions. Compared with the free DHA group with 31.75% of A549-TAX cell apoptosis, the percentage of apoptotic cells was approximately 76.67% in the D-ZIF group. D-ZIF inhibited tumor growth by inducing tumor cell apoptosis through the mechanism of ROS production and regulation of Nrf2/HO-1 and P38 MAPK signaling pathways. D-ZIF showed potent effects in treating tumors with high safety in vivo. Conclusion: This pH-responsive release mechanism enhanced the targeting efficiency of DHA towards tumor cells, thereby increasing drug concentration in tumor sites with negligible side effects. Herein, D-ZIF holds great promise for curing cancers with minimal adverse effects.

Renal thrombotic microangiopathy is associated with poor renal survival in children with immunoglobulin A nephropathy.

AIM: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients. METHODS: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non-rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed. RESULTS: IgAN-rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P = .016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P = .025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P = .037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non-rTMA group (χ2 = 18.467, P = .000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P = .037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P = .027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P = .041) were identified as independent risk factors for the development of end-stage renal disease (ESRD). CONCLUSION: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN.

Rapid response to fifth-line brigatinib plus entrectinib in an ALK-rearranged lung adenocarcinoma with an acquired ETV6-NTRK3 fusion: a case report.

The management of non-small cell lung cancer (NSCLC), specifically targeting the anaplastic lymphoma kinase (ALK) with tyrosine kinase inhibitors (TKIs), is challenged by the emergence of therapeutic resistance. Resistance mechanisms to ALK TKIs can be broadly classified into ALK-dependent and ALK-independent pathways. Here, we present a case with lung adenocarcinoma (LUAD) harboring an ALK rearrangement. The patient had developed resistance to sequential ALK TKI therapies, with an acquired ETV6-NTRK3 (E4:N14) fusion as a potential mechanism of ALK-independent resistance to lorlatinib. Subsequently, the patient was treated with the combination of brigatinib plus entrectinib and demonstrated a positive response, achieving an 8-month progression-free survival. Our case provides a potential treatment option for LUAD patients with ALK rearrangements and highlights the utility of next-generation sequencing (NGS) in uncovering genetic alterations that can guide the selection of effective treatment strategies.

Extracellular Vesicles Derived from Neutrophils Accelerate Bone Regeneration by Promoting Osteogenic Differentiation of BMSCs.

The reconstruction of bone defects has been associated with severe challenges worldwide. Nowadays, bone marrow mesenchymal stem cell (BMSC)-based cell sheets have rendered this approach a promising way to facilitate osteogenic regeneration in vivo. Extracellular vesicles (EVs) play an essential role in intercellular communication and execution of various biological functions and are often employed as an ideal natural endogenous nanomedicine for restoring the structure and functions of damaged tissues. The perception of polymorphonuclear leukocytes (neutrophils, PMNs) as indiscriminate killer cells is gradually changing, with new evidence suggesting a role for these cells in tissue repair and regeneration, particularly in the context of bone healing. However, the role of EVs derived from PMNs (PMN-EVs) in bone regeneration remains largely unknown, with limited research being conducted on this aspect. In the current study, we investigated the effects of PMN-EVs on BMSCs and the underlying molecular mechanisms as well as the potential application of PMN-EVs in bone regeneration. Toward this end, BMSC-based cell sheets with integrated PMN-EVs (BS@PMN-EVs) were developed for bone defect regeneration. PMN-EVs were found to significantly enhance the proliferation and osteogenic differentiation of BMSCs in vitro. Furthermore, BS@PMN-EVs were found to significantly accelerate bone regeneration in vivo by enhancing the maturation of the newly formed bone in rat calvarial defects; this is likely attributable to the effect of PMN-EVs in promoting the expression of key osteogenic proteins such as SOD2 and GJA1 in BMSCs. In conclusion, our findings demonstrate the crucial role of PMN-EVs in promoting the osteogenic differentiation of BMSCs during bone regeneration. Furthermore, this study proposes a novel strategy for enhancing bone repair and regeneration via the integration of PMN-EVs with BMSC-based cell sheets.

Fuzhengjiedu San inhibits porcine reproductive and respiratory syndrome virus by activating the PI3K/AKT pathway.

BACKGROUND: Traditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear. METHODS: In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS's action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis. RESULTS: Network pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway. CONCLUSION: We conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation.

Effects of micro/nanoplastics on oxidative damage and serum biochemical parameters in rats and mice: a meta-analysis.

Micro/nanoplastics (MNPs) are emerging as environmental pollutants with potential threats to human health. The accumulation of MNPs in the body can cause oxidative stress and increase the risk of cardiovascular disease (CVD). With the aim to systematically evaluate the extent of MNPs-induced oxidative damage and serum biochemical parameters in rats and mice, a total of 36 eligible articles were included in this meta-analysis study. The results reported that MNPs can significantly increase the levels of oxidants such as reactive oxygen species (ROS) and malondialdehyde (MDA) (P < 0.05), and resulted in notable increase in serum biochemical parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05). Conversely, MNPs significantly reduced levels of antioxidants such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) (P < 0.05). Subgroup analysis revealed that smaller MNPs with oral administration and prolonged treatment, were associated with more pronounced oxidative stress and enhanced serum biochemical parameters alteration. In addition, after affected by MNPs, the levels of ALT and AST in liver group (SMD = 2.26, 95% CI = [1.59, 2.94] and SMD = 3.10, 95% CI = [1.25, 4.94]) were higher than those in other organs. These comprehensive results provide a scientific foundation for devising strategies to prevent MNPs-induced damage, contributing to solution of this environmental and health challenge.

Stereoelectroencephalography-guided radiofrequency thermocoagulation of the epileptogenic zone: a potential treatment and prognostic indicator for subsequent excision surgery.

PURPOSE: To evaluate the safety and efficacy of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) for drug-resistant focal epilepsy and investigate the relationship between post-RFTC remission duration and delayed excision surgery effectiveness. METHODS: We conducted a retrospective analysis of 43 patients with drug-resistant focal epilepsy who underwent RFTC via SEEG electrodes. After excluding three, the remaining 40 were classified into subgroups based on procedures and outcomes. Twenty-four patients (60%) underwent a secondary excision surgery. We determined the predictive value of RFTC outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the duration of seizure freedom after RFTC were assessed. RESULTS: Among 40 patients, 20% achieved Engel class I with RFTC alone, while 24 underwent delayed secondary excision surgery. Overall, 41.7% attained Engel class I, with a 66.7% success rate combining RFTC with delayed surgery. Seizure freedom duration was significantly longer in the success group (mean 4.9 months, SD = 2.7) versus the failure group (mean 1.9 months, SD = 1.1; P = 0.007). A higher proportion of RFTC-only and delayed surgical success group patients had preoperative lesional findings (p = 0.01), correlating with a longer time to seizure recurrence (p < 0.05). Transient postoperative complications occurred in 10%, resolving within a year. CONCLUSION: This study demonstrates that SEEG-guided RFTC is a safe and potential treatment option for patients with drug-resistant focal epilepsy. A prolonged duration of seizure freedom following RFTC may serve as a predictive marker for the success of subsequent excision surgery.

Effects of Exposure to Conflicting Health Information on Topic-Specific Information Sharing and Seeking Intentions.

Despite considerable evidence that exposure to conflicting health information can have undesirable effects on outcomes including public understanding about and trust in health recommendations, comparatively little is known about whether such exposure influences intentions to engage in two communication behaviors central to public health promotion: information sharing and information seeking. The purpose of the current study is to test whether exposure to conflicting information influences intentions to share and seek information about six health topics. We analyzed data from two waves of a longitudinal survey experiment with a nationally representative sample of U.S. adults (N = 3,920). Participants were randomly assigned to either a conflict or no-conflict message condition, in which they read news stories and social media posts about three (of six) randomly selected health topics at Time 1 and the remaining three at Time 2. The dependent variables, which were measured at Time 2, asked participants whether they intended to share or seek information about the three topics they had just viewed. Linear mixed effects models showed that exposure to conflict reduced intentions to share and seek information, regardless of health topic. These findings suggest that exposure to conflicting health information discourages two important types of health information engagement, thus adding to the growing evidence base documenting the adverse consequences of conflicting information for public health.

Effect of Prosocial Behaviors on e-Consultations in a Web-Based Health Care Community: Panel Data Analysis.

BACKGROUND: Patients using web-based health care communities for e-consultation services have the option to choose their service providers from an extensive digital market. To stand out in this crowded field, doctors in web-based health care communities often engage in prosocial behaviors, such as proactive and reactive actions, to attract more users. However, the effect of these behaviors on the volume of e-consultations remains unclear and warrants further exploration. OBJECTIVE: This study investigates the impact of various prosocial behaviors on doctors' e-consultation volume in web-based health care communities and the moderating effects of doctors' digital and offline reputations. METHODS: A panel data set containing information on 2880 doctors over a 22-month period was obtained from one of the largest web-based health care communities in China. Data analysis was conducted using a 2-way fixed effects model with robust clustered SEs. A series of robustness checks were also performed, including alternative measurements of independent variables and estimation methods. RESULTS: Results indicated that both types of doctors' prosocial behaviors, namely, proactive and reactive actions, positively impacted their e-consultation volume. In terms of the moderating effects of external reputation, doctors' offline professional titles were found to negatively moderate the relationship between their proactive behaviors and their e-consultation volume. However, these titles did not significantly affect the relationship between doctors' reactive behaviors and their e-consultation volume (P=.45). Additionally, doctors' digital recommendations from patients negatively moderated both the relationship between doctors' proactive behaviors and e-consultation volume and the relationship between doctors' reactive behaviors and e-consultation volume. CONCLUSIONS: Drawing upon functional motives theory and social exchange theory, this study categorizes doctors' prosocial behaviors into proactive and reactive actions. It provides empirical evidence that prosocial behaviors can lead to an increase in e-consultation volume. This study also illuminates the moderating roles doctors' digital and offline reputations play in the relationships between prosocial behaviors and e-consultation volume.

Lentinus edodes mycelium polysaccharide inhibits AGEs-induced HUVECs pyroptosis by regulating LncRNA MALAT1/miR-199b/mTOR axis and NLRP3/Caspase-1/GSDMD pathway.

A novel Lentinus edodes mycelia polysaccharide (LMP) prepared in our laboratory has been identified to be effective in inhibiting the damage of islet ß cells induced by glucose toxicity. However, whether it can effectively alleviate the pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by advanced glycation end products (AGEs) remains unclear. Bioinformatics and cell biology techniques were used to explore the mechanism of LMP inhibiting AGEs-induced HUVECs damage. The results indicated that AGEs significantly increased the expression of LncRNA MALAT1, decreased cell viability to 79.67 %, increased intracellular ROS level to 248.19 % compared with the control group, which further led to cell membrane rupture. The release of LDH in cellular supernatant was increased to 149.42 %, and the rate of propidium iodide staining positive cells increased to 277.19 %, indicating the cell pyroptosis occurred. However, the above trend was effectively retrieved after the treatment with LMP. LMP effectively decreased the expression of LncRNA MALAT1 and mTOR, promoted the expression of miR-199b, inhibited AGEs-induced HUVECs pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway. LncRNA MALAT1 might be a new target for LMP to inhibit AGEs-induced HUVECs pyroptosis. This study manifested the role of LMP in improving diabetes angiopathy and broadens the application of polysaccharide.

Enzymatic characterization and thermostability improvement of an acidophilic endoxylanase PphXyn11 from Paenibacillus physcomitrellae XB.

GH11 enzyme is known to be specific and efficient for the hydrolysis of xylan. It has been isolated from many microorganisms, and its enzymatic characteristics and thermostability vary between species. In this study, a GH11 enzyme PphXyn11 from a novel xylan-degrading strain of Paenibacillus physcomitrellae XB was characterized, and five mutants were constructed to try to improve the enzyme's thermostability. The results showed that PphXyn11 was an acidophilic endo-ß-1,4-xylanase with the optimal reaction pH of 3.0-4.0, and it could deconstruct different kinds of xylan substrates efficiently, such as beechwood xylan, wheat arabinoxylan and xylo-oligosaccharides, to produce xylobiose and xylotriose as the main products at the optimal reaction temperature of 40 °C. Improvement of the thermal stability of PphXyn11 using site-directed mutagenesis revealed that three mutants, W33C/N47C, S127C/N174C and S49E, designed by adding the disulfide bonds at the N-terminal, C-terminal and increasing the charged residues on the surface of PphXyn11 respectively, could increase the enzymatic activity and thermal stablility significantly and make the optimal reaction temperature reach 50 °C. Molecular dynamics simulations as well as computed the numbers of salt bridges and hydrogen bonds indicated that the protein structures of these three mutants were more stable than the wild type, which provided theoretical support for their improved thermal stability. Certainly, further research is necessary to improve the enzymatic characteristics of PphXyn11 to achieve the bioconversion of hemicellulosic biomass on an applicable scale.

First Report of Alternaria alternata Causing Leaf Spot on Smooth Bromegrass (Bromus inermis Leyss.) in China.

Smooth bromegrass (Bromus inermis Leyss.) is an important forage crop in northern China. In July 2021, leaf spot symptoms were observed on smooth bromegrass in Ewenki Banner, Hulunbuir, Inner Mongolia. In an area of approximately 0.12 hectares, 95% disease incidence was observed. Ten diseased plants were collected for pathogen isolation. Leaf tissues near the lesions were cut into 5 × 5 mm pieces, surface-disinfested in 75% ethanol for 3 min, and rinsed with sterile distilled water. The pieces were placed on water agar in petri plates and incubated at 25℃ for three days. The resulting colonies were flushed with sterile water and a spore suspension was serially diluted and plated on potato dextrose agar (PDA). A single-spore colony was obtained. Ten isolates were obtained and designated HE1 to HE10. The colony morphology was identical for all isolates, grayish white in color on the upper surface and light black on the underside. The mycelia were light gray and velvety. Conidia were light brown to brown in color and oblate, oblong or oval. The conidial dimensions were typically between 15 to 43 µm by 8 to 9 µm in size. The conidia possessed one to six transverse septa, with slight to distinct constrictions at each division, and zero to two longitudinal septa. These morphological characteristics resembled Alternaria alternata (Fr.) Keissl.. DNA was extracted from three isolates, HE3, HE4 and HE5, using the CTAB method. Polymerase chain reaction (PCR) was performed on the extracted DNA with a set of primers ITS1/ITS4, H31a/H31b, gpd1/gpd2, TEF1-728F/TEF1-986R, and RPB2-5F2/fRPB2-7cR. The amplicon sequences from the three isolates were analyzed using the BLAST in GenBank (https://www.ncbi.nlm.nih.gov/). The results showed a high sequence identity, ranging from 99 to 100%, with the A. alternata strain YTMZ-20-2 across all the genetic markers tested. The strong match reinforced the identification of the strains as A. alternata. The sequences were deposited in GenBank (Table S1). The three fungal isolates were identified as A. alternata based on their morphological and genetic data. To conduct Koch's postulates, the representative isolate HE4 was used. Smooth bromegrass seed was soaked in water for four days and sown in potting soil contained in plastic pots (10 cm diameter × 15 cm height, five seeds/pot) in a greenhouse under a 16-h photoperiod at temperatures between 20 to 25°C and 60% relative humidity. When the plants reached a height of approximately 20 cm, the plants in three pots (replicates) were sprayed with a spore suspension (106 conidial/ml) at 10 ml/pot, and three pots were sprayed with sterile water for control. Five days after inoculation, the plants exhibited leaf spot symptoms similar to those previously described, while the control plants remained unaffected. The causative fungus was successfully re-isolated from the diseased plants and confirmed morphologically and molecularly on its identity as described above. This experiment was independently conducted three times. This is the first report of A. alternata causing leaf spot on smooth bromegrass in China. Since there is risk that the disease could seriously reduce the yield of the forage crop smooth bromegrass, further research is needed.

Portable robots for upper-limb rehabilitation after stroke: a systematic review and meta-analysis.

BACKGROUND: Robot-assisted upper-limb rehabilitation has been studied for many years, with many randomised controlled trials (RCTs) investigating the effects of robotic-assisted training on affected limbs. The current trend directs towards end-effector devices. However, most studies have focused on the effectiveness of rehabilitation devices, but studies on device sizes are relatively few. GOAL: Systematically review the effect of a portable rehabilitation robot (PRR) on the rehabilitation effectiveness of paralysed upper limbs compared with non-robotic therapy. METHODS: A meta-analysis was conducted on literature that included the Fugl-Meyer Assessment (FMA) obtained from the PubMed and Web of Science (WoS) electronic databases until June 2023. RESULTS: A total of 9 studies, which included RCTs, were completed and a meta-analysis was conducted on 8 of them. The analysis involved 295 patients. The influence on upper-limb function before and after treatment in a clinical environment is analysed by comparing the experimental group using the portable upper-limb rehabilitation robot with the control group using conventional therapy. The result shows that portable robots prove to be effective (FMA: SMD = 0.696, 95% = 0.099 to.293, p < 0.05). DISCUSSION: Both robot-assisted and conventional rehabilitation effects are comparable. In some studies, PRR performs better than conventional rehabilitation, but conventional treatments are still irreplaceable. Smaller size with better portability has its advantages, and portable upper-limb rehabilitation robots are feasible in clinical rehabilitation. CONCLUSION: Although portable upper-limb rehabilitation robots are clinically beneficial, few studies have focused on portability. Further research should focus on modular design so that rehabilitation robots can be decomposed, which benefits remote rehabilitation and household applications.

Interpretable machine learning-based clinical prediction model for predicting lymph node metastasis in patients with intrahepatic cholangiocarcinoma.

OBJECTIVE: Prediction of lymph node metastasis (LNM) for intrahepatic cholangiocarcinoma (ICC) is critical for the treatment regimen and prognosis. We aim to develop and validate machine learning (ML)-based predictive models for LNM in patients with ICC. METHODS: A total of 345 patients with clinicopathological characteristics confirmed ICC from Jan 2007 to Jan 2019 were enrolled. The predictors of LNM were identified by the least absolute shrinkage and selection operator (LASSO) and logistic analysis. The selected variables were used for developing prediction models for LNM by six ML algorithms, including Logistic regression (LR), Gradient boosting machine (GBM), Extreme gradient boosting (XGB), Random Forest (RF), Decision tree (DT), Multilayer perceptron (MLP). We applied 10-fold cross validation as internal validation and calculated the average of the areas under the receiver operating characteristic (ROC) curve to measure the performance of all models. A feature selection approach was applied to identify importance of predictors in each model. The heat map was used to investigate the correlation of features. Finally, we established a web calculator using the best-performing model. RESULTS: In multivariate logistic regression analysis, factors including alcoholic liver disease (ALD), smoking, boundary, diameter, and white blood cell (WBC) were identified as independent predictors for LNM in patients with ICC. In internal validation, the average values of AUC of six models ranged from 0.820 to 0.908. The XGB model was identified as the best model, the average AUC was 0.908. Finally, we established a web calculator by XGB model, which was useful for clinicians to calculate the likelihood of LNM. CONCLUSION: The proposed ML-based predicted models had a good performance to predict LNM of patients with ICC. XGB performed best. A web calculator based on the ML algorithm showed promise in assisting clinicians to predict LNM and developed individualized medical plans.

Photoredox-catalyzed carbonylative acylation of styrenes with Hantzsch esters.

Ketones exist widely in naturally occurring products and are indispensable building blocks in organic synthesis. Carbonylation represents one of the most straightforward methods for ketone preparation and has become an attractive field in modern organic chemistry as well. Among the strategies, photocatalytic carbonylation is also worthy of further exploration. Herein, we developed a three-component carbonylation that provides a new method for the synthesis of ketones from Hantzsch esters, CO and styrenes. The reaction was performed under a blue light environment and yields a series of ketones with moderate to good yields.

Sphingomonas lacusdianchii sp. nov., an attached bacterium inhibited by metabolites from its symbiotic cyanobacterium.

An alpha-proteobacterial strain JXJ CY 53 T was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) collected from Lake Dianchi, China. JXJ CY 53 T was observed to be an aerobic, Gram-stain-negative, oval shaped, and mucus-secreting bacterium. It had C18:1ω7c and C16:0 as the major cellular fatty acids, Q-10 as the predominant ubiquinone, and sphingoglycolipid, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylmethylethanolamine as the polar lipids. The G + C content of DNA was 65.85%. The bacterium had 16S rRNA gene sequence identities of 98.9% and 98.7% with Sphingomonas panni DSM 15761 T and Sphingomonas hankookensis KCTC 22579 T, respectively, while less than 97.4% identities with other members of the genus. Further taxonomic analysis indicated that JXJ CY 53 T represented a new member of Sphingomonas, and the species epithet was proposed as Sphingomonas lacusdianchii sp. nov. (type strain JXJ CY 53 T = KCTC 72813 T = CGMCC 1.17657 T). JXJ CY 53 T promoted the growth of MF-905 by providing bio-available phosphorus and nitrogen, plant hormones, vitamins, and carotenoids. It could modulate the relative abundances of nonculturable bacteria associated with MF-905 and influence the interactions of MF-905 and other bacteria isolated from the cyanobacterium, in addition to microcystin production characteristics. Meanwhile, MF-905 could provide JXJ CY 53 T dissolved organic carbon for growth, and control the growth of JXJ CY 53 T by secreting specific chemicals other than microcystins. Overall, these results suggest that the interactions between Microcystis and its attached bacteria are complex and dynamic, and may influence the growth characteristics of the cyanobacterium. This study provided new ideas to understand the interactions between Microcystis and its attached bacteria. KEY POINTS: • A novel bacterium (JXJCY 53 T) was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) • JXJCY 53 T modulated the growth and microcystin production of MF-905 • MF-905 could control the attached bacteria by specific chemicals other than microcystins (MCs).