A High-Rate and Ultrastable Re2Te5/MXene Anode for Potassium Storage Enabled by Amorphous/Crystalline Heterointerface Engineering.

The pursuit of anode materials capable of rapid and reversible potassium storage performance is a challenging yet fascinating target. Herein, a heterointerface engineering strategy is proposed to prepare a novel superstructure composed of amorphous/crystalline Re2Te5 anchored on MXene substrate (A/C-Re2Te5/MXene) as an advanced anode for potassium-ion batteries (KIBs). The A/C-Re2Te5/MXene anode exhibits outstanding reversible capacity (350.4 mAh g-1 after 200 cycles at 0.2 A g-1), excellent rate capability (162.5 mAh g-1 at 20 A g-1), remarkable long-term cycling capability (186.1 mAh g-1 at 5 A g-1 over 5000 cycles), and reliable operation in flexible full KIBs, outperforming state-of-the-art metal chalcogenides-based devices. Experimental and theoretical investigations attribute this high performance to the synergistic effect of the A/C-Re2Te5 with a built-in electric field and the elastic MXene, enabling improved pseudocapacitive contribution, accelerated charge transfer behavior, and high K+ ion adsorption/diffusion ability. Meanwhile, a combination of intercalation and conversion reactions mechanism is observed within A/C-Re2Te5/MXene. This work offers a new approach for developing metal tellurides- and MXene-based anodes for achieving stable cyclability and fast-charging KIBs.

A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer.

BACKGROUND: F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). METHODS: This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. RESULTS: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 - 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. CONCLUSIONS: A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Construction and characterization of sodium alginate/polyvinyl alcohol double-network hydrogel beads with surfactant-tailored adsorption capabilities for efficient tetracycline hydrochloride removal.

The extensive use of tetracycline (TC) for disease control and the residuals in wastewater has resulted in the spread and accumulation of antibiotic resistance genes, posing a severe threat to the human health and environmental safety. To solve this problem, a series of double-network hydrogel beads based on sodium alginate and polyvinyl alcohol were constructed with the introduction of various surfactants to modulate the morphology. The results showed that the introduction of surfactants can modulate the surface morphology and internal structure, which can also regulate the adsorption ability of the hydrogel beads. The SDS-B beads with SDS as surfactant exhibited highest adsorption efficiency for removal of TC with a maximum adsorption capacity up to 121.6 mg/g, which possessed a resistance to various cations and humic acid. The adsorption mechanism revealed that the superior adsorption performance of the hydrogel beads was primarily attributed to hydrogen bonding, electrostatic attraction, and π-π EDA interactions. Adsorption kinetics demonstrated that the pseudo-second-order model fitted the adsorption process well and adsorption isotherm showed the adsorption of TC occurred through both chemical and physical interactions. Moreover, the adsorption efficiency remained approximately 87.5 % after three adsorption-desorption cycles, which may have potential application and practical value in TC adsorption.

Association between widowhood and cognitive function among Chinese older adults with hearing impairment: the moderating effect of social support and participation.

BACKGROUND: Older adults with hearing impairments are vulnerable to cognitive impairment. Although previous reports suggest a correlation between widowhood and cognitive impairment, further investigation is needed to elucidate the effect of widowhood on cognitive function and the moderating effects of social support and participation on widowhood-related cognitive impairment in this vulnerable demographic. METHODS: The study's data were sourced from the nationally representative Chinese Longitudinal Healthy Longevity Survey (CLHLS) for the years 2011, 2014, and 2018. Multiple linear regression was used to analyze the association between widowhood and cognitive function among older adults. Multivariate logistic regression examined the effect of widowhood on the likelihood of experiencing various levels of cognitive impairment in older adults with hearing impairments. A moderating effect model explored the roles of social support and participation in mitigating widowhood-related cognitive impairment. RESULTS: The cognitive function of older adults with hearing impairment was found to be lower than that of those without hearing impairment. Widowhood was significantly negatively correlated with Mini-Mental State Examination (MMSE) scores in older adults, both with (Coef. = -0.898) and without (Coef.: = -0.680) hearing impairments. A stronger association was observed between widowhood and declining cognitive function among older adults with hearing impairment. Specifically, widowhood may be more likely to significantly increase the likelihood of moderate and severe cognitive impairment (RRR = 1.326, 1.538) among older adults with hearing impairments. Social support and social participation significantly moderated the cognitive impairment associated with widowhood among hearing-impaired older adults. These forms of support and engagement are buffers against the risk of widowhood-related cognitive impairment among this demographic. CONCLUSIONS: Our findings indicate that widowhood is significantly associated with cognitive impairment in older adults with hearing impairment. Social support and participation help mitigate this risk. Strategies should prioritize early screening, specialized cognitive rehabilitation, comprehensive care, and enhancing social support and participation to maintain cognitive health in this vulnerable population following widowhood.

Examining the Relationship Between Social Support, Self-Efficacy, Diabetes Self-Management, and Quality of Life Among Rural Individuals With Type 2 Diabetes in Eastern China: Path Analytical Approach.

BACKGROUND: Patients with type 2 diabetes (T2D) in rural China frequently exhibit inadequate diabetes self-management (DSM) and a reduced quality of life (QoL). Social support and self-efficacy are known to influence DSM and QoL. However, the pathways through which social support and self-efficacy impact DSM and QoL among patients with T2D in rural China has yet to be fully elucidated. OBJECTIVE: This study offers a foundation for developing policies in rural chronic disease management, thereby, contributing to the improvement of T2D prevention and control in China and other transitional countries. METHODS: This study used a cross-sectional design, collecting data from a survey conducted between May and July 2021 on DSM and QoL among rural patients diagnosed with T2D in 2 townships in East China. All patients with T2D were enrolled through cluster sampling from the township health center database, and a questionnaire survey was administered by investigators. Structural equation modeling and multiple regression analyses were used to explore the pathways through which social support influences DSM and QoL, as well as the mediating role of self-efficacy. RESULTS: It was found that the DSM score (mean 37.42, SD 7.70) was less than half of the maximum theoretical score. The QoL score (mean 48.92, SD 8.88) accounted for 36% of the maximum theoretical score. Social support directly and positively affected the DSM and QoL of Chinese rural patients with T2D (P<.01); an increase of 1 unit in social support was associated with a direct increment of 0.339 units in DSM and 0.397 units in QoL. Self-efficacy played a positive mediating role (P<.01), further increasing DSM and QoL by 0.147 and 0.159 units, respectively. The mediating effect of self-efficacy accounted for 30.2% and 28.6% of the total effect of social support on DSM and QoL. Furthermore, the family and friend dimension of social support, along with the symptom and disease management dimensions of self-efficacy, were significantly associated with DSM or QoL (P<.01). CONCLUSIONS: The study confirmed the direct and indirect influences of social support on DSM and QoL and elucidated the mediating effect of self-efficacy among rural patients with T2D in eastern China. Interventions should be developed to enhance both social support and self-efficacy, creating a positive cycle of mutual reinforcement to improve DSM and QoL among this group.

Degradation of phenol by metal-free electro-fenton using a carbonyl-modified activated carbon cathode: Promoting simultaneous H2O2 generation and activation.

The low yield of hydrogen peroxide, narrow pH application range, and secondary pollution due to iron sludge precipitation are the major drawbacks of the electro-Fenton (EF) process. Metal-free electro-Fenton technology based on carbonaceous materials is a promising green pollutant degradation technology. Activated carbon cathodes enriched with carbonyl functional groups were prepared using a two-step annealing method for the degradation of phenol pollutants. The •OH in the activation process of H2O2 were identified using the EPR test technique. The action mechanism of carbonyl groups on H2O2 activation was investigated in conjunction with density functional theory (DFT) calculations. The EPR tests demonstrated that the modified activated carbon could promote the in-situ activation of H2O2 to •OH. And the results of material analysis and DFT showed that C=O could facilitate the activation of hydrogen peroxide through the electron transfer mechanism as an electron-donating group. Electrochemical tests showed that both the oxygen reduction activity and 2e-ORR selectivity of the modified activated carbons were significantly improved. Compared with the original activated carbon cathode and EF, the degradation efficiency of phenol in the ACNH-1000/GF cathode was increased by 58.10% and 45.61%, respectively. Compared with EF, ACNH-1000/GF metal-free electro-Fenton effectively expands the pH application range, and is proven to be less affected by solution initial pH, while avoiding secondary pollution. The metal-free electro-Fenton system can save more than a quarter of the cost of EF system. This study has a deep understanding of the reaction mechanism of the carbonyl modified activated carbon, and provides valuable insights for the design of metal-free catalysts, so as to promote its application in the degradation of organic pollutants.

Optimization Strategy for Formaldehyde Removal by Carbon Cathode Electro-Fenton: Enhancement of Formaldehyde and Oxygen Co-adsorption by Rational Nitrogen Doping Types.

This study investigates the effect of N-doped coal-based activated carbon cathode on formaldehyde-oxygen coadsorption. Further investigation investigates the effect of formaldehyde-oxygen coadsorption on H2O2 generation and formaldehyde removal in an electro-Fenton system. Nitrogen doping enhances formaldehyde and oxygen coadsorption by modulating competitive adsorption. Density Functional Theory (DFT) calculations confirm pyrrole nitrogen favors formaldehyde, and graphite nitrogen favors oxygen adsorption. N-doped activated carbon adsorbs 0.36 mg of formaldehyde and 0.1 mg of oxygen in 120 min and removes 82.43% of formaldehyde after electro-Fenton treatment. N-doped activated carbon enhances the synergistic adsorption of formaldehyde and oxygen. In the synergistic adsorption process, the amount of formaldehyde adsorbed is greater than the amount of oxygen adsorbed. This improves the removal efficiency of formaldehyde by electro-Fenton technology. It provides a new method for electro-Fenton removal of organic pollutants.

Dual mass spectrometry imaging and spatial metabolomics to investigate the metabolism and nephrotoxicity of nitidine chloride.

Evaluating toxicity and decoding the underlying mechanisms of active compounds are crucial for drug development. In this study, we present an innovative, integrated approach that combines air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and spatial metabolomics to comprehensively investigate the nephrotoxicity and underlying mechanisms of nitidine chloride (NC), a promising anti-tumor drug candidate. Our quantitive AFADESI-MSI analysis unveiled the region specific of accumulation of NC in the kidney, particularly within the inner cortex (IC) region, following single and repeated dose of NC. High spatial resolution ToF-SIMS analysis further allowed us to precisely map the localization of NC within the renal tubule. Employing spatial metabolomics based on AFADESI-MSI, we identified over 70 discriminating endogenous metabolites associated with chronic NC exposure. These findings suggest the renal tubule as the primary target of NC toxicity and implicate renal transporters (organic cation transporters, multidrug and toxin extrusion, and organic cation transporter 2 (OCT2)), metabolic enzymes (protein arginine N-methyltransferase (PRMT) and nitric oxide synthase), mitochondria, oxidative stress, and inflammation in NC-induced nephrotoxicity. This study offers novel insights into NC-induced renal damage, representing a crucial step towards devising strategies to mitigate renal damage caused by this compound.

A multicenter, open-label, parallel-group, randomized controlled trial of Tongluo-Qutong rubber plaster for the treatment of cervical spondylotic radiculopathy.

BACKGROUND: In China, Tongluo-Qutong rubber plaster (TQRP) is commonly used for cervical spondylotic radiculopathy, but lacks high-quality trials. OBJECTIVE: This study aimed to conduct a multicenter, open-label, parallel-group, randomized controlled trial in China to investigate the practical efficacy and safety of TQRP in the treatment of CSR. METHODS: A total of 240 patients diagnosed with CSR were recruited for the investigation from multiple hospitals in Gansu province, China. The patients were randomly assigned to either an experimental or a control group. The experimental group received treatment with TQRP, whereas the control group was administered a diclofenac sodium patch (DSP) for a maximum duration of 21 days. The visual analogue scale (VAS) score for pain, the proportion of patients experiencing 50% or more pain relief, the neck disability index (NDI), changes as per the Eaton trial, and recurrence during the follow-up period were evaluated for both groups. The safety and adverse events associated with the concurrent drug therapy were also evaluated. RESULTS: At each time point, the mean VAS and NDI scores of both groups demonstrated a downward trend. The experimental group exhibited a greater decline in VAS score at each time point compared to the control group (P< 0.01). In the Eaton trial, both the percentage of patients experiencing pain relief of 50% or more and the number of abnormal results exhibited improvement. However, the outcomes in the 21 ± 3d experimental group were significantly superior to those in the control group (P< 0.01). During the follow-up period, the recurrence events in the experimental group were reduced compared to the control group. The difference between the two groups was statistically significant (P< 0.05). The incidence of adverse reactions was 1.74% for TQRP and 3.54% for DSP. CONCLUSION: TQRP is effective and safe in the treatment of CSR.

Pharmacometabolomics and mass spectrometry imaging approach to reveal the neurochemical mechanisms of Polygala tenuifolia.

Polygala tenuifolia, commonly known as Yuanzhi (YZ) in Chinese, has been shown to possess anti-insomnia properties. However, the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear. Herein, we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging (MSI)-based spatial resolved metabolomics. According to the results, 17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain, which might be the major components contributing to the sedative-hypnotic effects. Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse, and dopaminergic synapse, among other pathways. LC-MS/MS-based targeted metabolomics and Western blot (WB) revealed that tryptophan-serotonin-melatonin (Trp-5-HT-Mel) and tyrosine-norepinephrine-adrenaline (Tyr-Ne-Ad) are the key regulated pathways. Dopa decarboxylase (DDC) upregulation and phenylethanolamine N-methyltransferase (PNMT) downregulation further confirmed these pathways. Furthermore, MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland (PG), and Ad in the brainstem, including the middle brain (MB), pons (PN), and hypothalamus (HY). In summary, this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine, YZ.

Maize zinc uptake is influenced by arbuscular mycorrhizal symbiosis under various soil phosphorus availabilities.

The antagonistic interplay between phosphorus (P) and zinc (Zn) in plants is well established. However, the molecular mechanisms mediating those interactions as influenced by arbuscular mycorrhizal (AM) symbiosis remain unclear. We investigated Zn concentrations, root AM symbiosis, and transcriptome profiles of maize roots grown under field conditions upon different P levels. We also validated genotype-dependent P-Zn uptake in selected genotypes from a MAGIC population and conducted mycorrhizal inoculation experiments using mycorrhizal-defective mutant pht1;6 to elucidate the significance of AM symbiosis in P-Zn antagonism. Finally, we assessed how P supply affects Zn transporters and Zn uptake in extraradical hyphae within a three-compartment system. Elevated P levels led to a significant reduction in maize Zn concentration across the population, correlating with a marked decline in AM symbiosis, thus elucidating the P-Zn antagonism. We also identified ZmPht1;6 is crucial for AM symbiosis and confirmed that P-Zn antagonistic uptake is dependent on AM symbiosis. Moreover, we found that high P suppressed the expression of the fungal RiZRT1 and RiZnT1 genes, potentially impacting hyphal Zn uptake. We conclude that high P exerts systemic regulation over root and AM hyphae-mediated Zn uptake in maize. These findings hold implications for breeding Zn deficiency-tolerant maize varieties.

Unlocking the critical roles of N, P Co-Doping in MXene for Lithium-Oxygen Batteries: Elevated d-Band center and expanded interlayer spacing.

The design and fabrication of bifunctional catalysts with high electrocatalytic activity and stability are critical for developing highly reversible Li-O2 batteries (LOBs). Herein, the N, P co-doped MXene (NP-MXene) is prepared by one-step annealing method and evaluated as bifunctional catalyst for LOBs. The results suggest that the P doping plays a crucial role in increasing interlayer distance of MXene, thereby effectively providing more active sites, fast mass transfer, and ample space for the deposition/decomposition of Li2O2. Moreover, the N doping can significantly elevate the d-band center of Ti, thereby remarkably improving the adsorption of reaction intermediates and accelerating the deposition/decomposition of Li2O2 films. Consequently, the MXene-based LOBs deliver an ultrahigh specific capacity of 13,995 mAh/g at 500 mA g-1, a discharge/charge voltage gap of 0.89 V, and a cycle life up to 523 cycles with a limited capacity of 1000 mAh/g at 500 mA g-1. Impressively, the as-fabricated flexible LOBs with NP-MXene cathode display excellent cycling stability and ability to continuously power LEDs even after bending. Our findings pave the road of heteroatom doped MXenes as next-generation electrodes for high-performance energy storage and conversion systems.

Neoadjuvant anthracycline followed by toripalimab combined with nab-paclitaxel in patients with early triple-negative breast cancer (NeoTENNIS): a single-arm, phase II study.

Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II-III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3-67.6) and 41 of 70 (58.6%, 95% CI 46.2-70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1-2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Circular RNAs as potential biomarkers for male severe sepsis.

Circular RNAs (circRNAs) play important roles in many human diseases. However, their role in the development of severe sepsis, a condition that remains one of the main causes of death in intensive care units, has not yet been defined. In this study, we interrogated the molecular mechanisms of circRNAs in severe sepsis. We profiled the expression levels of 5,680 circRNAs in plasma extracted from blood samples of 9 severe sepsis cases or 9 controls (male, age 78 ± 7) using the Human circRNA Array. To enrich protein-coding genes hosting severe sepsis-related circRNAs, we conducted gene ontology and pathways analyses. Out of the identified 760 differentially expressed circRNAs, 404 were upregulated while 356 were downregulated (fold change [FC] ≥2 or ≤-2, and false discovery ratio <0.05). Circ-0008285 (located in exons of CDYL), showed significant upregulation in severe sepsis with an FC of 13.7, and Bonferroni-corrected P < 0.05/5. In silico analysis identified Circ-0008285 interacting microRNAs as well as protein-coding genes. We systematically investigated the differential expression pattern of circRNAs in severe sepsis. The circRNAs we identified might serve as potential biomarkers for diagnosis and prognosis of sepsis.

QL1209 (pertuzumab biosimilar) versus reference pertuzumab plus trastuzumab and docetaxel in neoadjuvant treatment for HER2-positive, ER/PR-negative, early or locally advanced breast cancer: A multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial.

BACKGROUND: This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative. METHODS: Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32. RESULTS: Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups. CONCLUSIONS: QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer. TRIAL REGISTRATION: Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

Bacillus coagulans restores pathogen-induced intestinal dysfunction via acetate-FFAR2-NF-κB-MLCK-MLC axis in Apostichopus japonicus.

Skin ulceration syndrome (SUS) is currently the main disease threatening Apostichopus japonicus aquaculture due to its higher mortality rate and infectivity, which is caused by Vibrio splendidus. Our previous studies have demonstrated that SUS is accompanied by intestinal microbiota (IM) dysbiosis, alteration of short-chain fatty acids (SCFAs) content and the damage to the intestinal barrier. However, the mediating effect of IM on intestine dysfunction is largely unknown. Herein, we conducted comprehensive intestinal microbiota transplantation (IMT) to explore the link between IM and SUS development. Furthermore, we isolated and identified a Bacillus coagulans strain with an ability to produce acetic acid from both healthy individual and SUS individual with IM from healthy donors. We found that dysbiotic IM and intestinal barrier function in SUS recipients A. japonicus could be restored by IM from healthy donors. The B. coagulans strain could restore IM community and intestinal barrier function. Consistently, acetate supply also restores intestinal homeostasis of SUS-diseased and V. splendidus-infected A. japonicus. Mechanically, acetate was found to specifically bind to its receptor-free fatty acid receptor 2 (FFAR2) to mediate IM structure community and intestinal barrier function. Knockdown of FFAR2 by transfection of specific FFAR2 siRNA could hamper acetate-mediated intestinal homeostasis in vivo. Furthermore, we confirmed that acetate/FFAR2 could inhibit V. splendidus-activated NF-κB-MLCK-MLC signaling pathway to restore intestinal epithelium integrity and upregulated the expression of ZO-1 and Occludin. Our findings provide the first evidence that B. coagulans restores pathogen-induced intestinal barrier dysfunction via acetate/FFAR2-NF-κB-MLCK-MLC axis, which provides new insights into the control and prevention of SUS outbreak from an ecological perspective.IMPORTANCESkin ulceration syndrome (SUS) as a main disease in Apostichopus japonicus aquaculture has severely restricted the developmental A. japonicus aquaculture industry. Intestinal microbiota (IM) has been studied extensively due to its immunomodulatory properties. Short-chain fatty acids (SCFAs) as an essential signal molecule for microbial regulation of host health also have attracted wide attention. Therefore, it is beneficial to explore the link between IM and SUS for prevention and control of SUS. In the study, the contribution of IM to SUS development has been examined. Additionally, our research further validated the restoration of SCFAs on intestinal barrier dysfunction caused by SUS via isolating SCFAs-producing bacteria. Notably, this restoration might be achieved by inhibition of NF-κB-MLCK-MLC signal pathway, which could be activated by V. splendidus. These findings may have important implications for exploration of the role of IM in SUS occurrence and provide insight into the SUS treatment.

Biodegradation of phenol-contaminated soil and plant growth promotion by Myroides xuanwuensis H13.

Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach. This study aims to screen for potential phenol-degrading bacteria and to verify the removal capacities of a selected strain in a bioaugmentation experiment at the greenhouse level using Brassica chinensis L. (Chinese cabbage) as the model plant and phenol-contaminated soil. In parallel, pot experiments were conducted using a collaborative approach based on this model system. We found that Myroides xuanwuensis strain H13 showed a high degradation capability, with a 97.67% efficiency in degrading 100 mg/L phenol. Under shaking flask conditions, H13 facilitated the solubilization of tricalcium phosphate and potassium feldspar powder. Pot experiments suggested a phenol removal percentage of 89.22% and enhanced availability of soil phosphorus and potassium for plants with H13 inoculation. In this case, the abundance of soil microbes and the activity of soil enzymes significantly increased as well. Furthermore, both photosynthesis and the antioxidant system in Chinese cabbage were enhanced following H13 inoculation, resulting in its increased yield and quality. Partial least squares path modeling revealed that H13 can primarily affect plant root growth, with a secondary impact on photosynthesis. These findings highlight the potential of biodegradation from phenol-degrading bacteria as a promising strategy for efficient phenol removal from soil while promoting plant growth and health.IMPORTANCEThis study is significant for environmental remediation and agriculture by its exploration of a more environmentally friendly and cost-effective bio-strategy in treating phenol-contaminated soil. These findings have essential implications for environmental remediation efforts and sustainable agriculture. By utilizing the biodegradation capabilities of Myroides xuanwuensis strain H13, it is possible to remove phenol contaminants from the soil efficiently, reducing their negative effects. Furthermore, the enhanced growth and health of the Chinese cabbage plants indicate the potential of this approach to promote sustainable crop production.

Exploring unmet healthcare needs and associated inequalities among middle-aged and older adults in Eastern China during the progression toward universal health coverage.

BACKGROUND: Given the rapid population aging in China, achieving universal health coverage (UHC) presents a primary challenge in addressing unmet healthcare needs and associated inequalities among middle-aged and older adults. Several studies have focused on healthcare utilization and its inequalities, but little attention has been paid to the inequality in unmet healthcare needs. This study aimed to analyze the inequalities in unmet the healthcare needs of middle-aged and older adults in eastern China during the progression toward UHC. METHODS: Data were obtained from the fourth, fifth, and sixth National Health Service Survey (NHSS) of Jiangsu Province, located in eastern China, during the years 2008, 2013, and 2018, respectively. Logistic regression models were used to assess the associated factors of unmet healthcare needs. The inequality was measured according to the concentration index (CI) and its decomposition. RESULTS: In this study, we found that 12.86%, 2.22%, and 48.89% of middle-aged and older adults reported unmet needs for outpatient and inpatient services and physical examinations, respectively. The prevalence of unmet outpatient needs increased from 2008 to 2018, while the prevalence of unmet inpatient services was lower but maintained. The prevalence of unmet needs for physical examinations among middle-aged and older adults markedly decreased since 2008. Rural areas had a higher prevalence of unmet needs for inpatient services and physical examinations than urban areas. Unmet healthcare needs were more prevalent among the poor. The pro-poor inequalities of unmet healthcare needs have been mitigated during the progression toward UHC; however, they remain predominant among rural middle-aged and older adults for outpatient and inpatient services. Socioeconomic factors significantly influenced unmet healthcare needs and contributed to their inequalities. CONCLUSIONS: The findings characterize the prevalence and inequality of unmet healthcare need among middle-aged and older adults in eastern China during the progression toward UHC. Policy interventions should be actively advocated to effectively mitigate the unmet healthcare needs and address the associated inequalities.

Stability and variability of molecular subtypes: comparative analysis of primary and metastatic triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive cancer. Although our previous study classified primary TNBC into four subtypes, comprehensive longitudinal investigations are lacking. METHODS: We assembled a large-scale, real-world cohort comprised of 880 TNBC patients [465 early-stage TNBC (eTNBC) and 415 metastatic TNBC (mTNBC) patients] who were treated at Fudan University Shanghai Cancer Center. The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort. Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes. RESULTS: The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1% (47/465). The median overall survival (OS) in the mTNBC cohort was 27.2 months [95% confidence interval (CI), 24.4-30.2 months], which indicated a poor prognosis. The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed. Consistent molecular subtypes were maintained in 77.5% of the patients throughout disease progression with the mesenchymal-like (MES) subtype demonstrating a tendency for subtype transition and brain metastasis. Additionally, a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial. CONCLUSIONS: Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression. However, we emphasize the major importance of repeat pathologic confirmation of the MES subtype.