miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency.

Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

Clinical implications of serum miR-34a in breast cancer and its predictive value for the efficacy of neoadjuvant chemotherapy.

OBJECTIVES: This study aims to explore the implications of serum miR-34a in breast cancer (BC) and its predictive value for the efficacy of neoadjuvant chemotherapy (NACT). METHODS: A retrospective analysis was performed on 102 female BC patients (research group) admitted to The Second Affiliated Hospital of Anhui Medical University between January 2016 to March 2018 and 102 concurrent female health controls who underwent physical examinations (control group). Serum samples from both groups were subjected to quantitative reverse transcription polymerase chain reaction to measure miR-34a expression. The correlation of miR-34a with BC patients' clinical parameters was analyzed, and the implications of miR-34a for diagnosing BC and predicting NACT efficacy were assessed by receiver operating characteristic curves. Logistic regression analysis was employed to determine whether miR-34a independently influenced treatment effectiveness and patient outcomes. RESULTS: The data showed significantly lower miR-34a levels in the research group than in the control group (P<0.05). The area under the curve (AUC) of miR-34a for differentiating BC was 0.888. In BC patients, miR-34a was strongly correlated with tumor staging and differentiation degree. Following NACT, BC patients showed an evident rise in miR-34a expression, with higher levels in patients with effective treatment compared to those with treatment failure (P<0.05). The AUC values of serum miR-34a in predicting the efficacy of neoadjuvant chemotherapy from FD to SD and from SD to TD were 0.880 and 0.861, respectively (P<0.001). Furthermore, patients with favorable prognosis exhibited markedly higher serum miR-34a expression than those with poor prognosis (P<0.05). The AUC of miR-34a expression for predicting adverse prognosis was 0.825. Decreased miR-34a was identified as an independent risk factor for treatment failure and poor prognosis. CONCLUSIONS: Taken together, serum miR-34a is downregulated in BC and can predict the clinical progression of BC patients and the therapeutic efficacy of NACT.

Highly Conductive and Stable Composite Polymer Electrolyte with Boron Nitride Nanotubes for All-Solid-State Lithium Metal Batteries.

All-solid-state lithium metal batteries (ASSLMBs) have emerged as the most promising next-generation energy storage devices. However, the unsatisfactory ionic conductivity of solid electrolytes at room temperature has impeded the advancement of solid-state batteries. In this work, a multifunctional composite solid electrolyte (CSE) is developed by incorporating boron nitride nanotubes (BNNTs) into polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP). BNNTs, with a high aspect ratio, trigger the dissociation of Li salts, thus generating a greater population of mobile Li+, and establishing long-distance Li+ transport pathways. PVDF-HFP/BNNT exhibits a high ionic conductivity of 8.0 × 10-4 S cm-1 at room temperature and a Li+ transference number of 0.60. Moreover, a Li//Li symmetric cell based on PVDF-HFP/BNNT demonstrates robust cyclic performance for 3400 h at a current density of 0.2 mA cm-2. The ASSLMB formed from the assembly of PVDF-HFP/BNNT with LiFePO4 and Li exhibits a capacity retention of 93.2% after 850 cycles at 0.5C and 25 °C. The high-voltage all-solid-state LiCoO2/Li cell based on PVDF-HFP/BNNT also exhibits excellent cyclic performance, maintaining a capacity retention of 96.4% after 400 cycles at 1C and 25 °C. Furthermore, the introduction of BNNTs is shown to enhance the thermal conductivity and flame retardancy of the CSE.

Association between Abortion and All-Cause and Cause-Specific Premature Mortality: A Prospective Cohort Study from the UK Biobank.

Background: Concerns have been raised about the increasing prevalence of both spontaneous and induced abortions worldwide, yet their effect on premature mortality remains poorly understood. We aimed to examine the associations between abortion and all-cause and cause-specific premature mortality, and the potential effect modification by maternal characteristics. Methods: Women aged 39 to 71 years at baseline (2006 to 2010) with prior pregnancies were derived from the UK Biobank and categorized as no abortion history, spontaneous abortion alone, induced abortion alone, and both spontaneous and induced abortions. All-cause and cause-specific mortality were ascertained through linkage to death certificate data, with premature death defined as occurring before the age of 70. Results: Of the 225,049 ever gravid women, 43,418 (19.3%) reported spontaneous abortion alone, 27,135 (12.1%) reported induced abortion alone, and 10,448 (4.6%) reported both spontaneous and induced abortions. During a median of 14.4 years of follow-up, 5,353 deaths were recorded, including 3,314 cancer-related and 1,444 cardiovascular deaths. Compared with no abortion history, spontaneous abortion alone was associated with an increased risk of all-cause premature mortality (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 1.02 to 1.17), and induced abortion alone was associated with increased risks of all-cause (aHR 1.12, 95% CI 1.04 to 1.22) and cardiovascular mortality (aHR 1.27, 95% CI 1.09 to 1.48). The aHRs for all-cause and cardiovascular mortality were higher for recurrent abortions, whether spontaneous or induced (P trend < 0.05). The increased risk of all-cause mortality associated with induced abortion was higher in women with hypertensive disorders of pregnancy than in those without (40% vs. 9%, P interaction = 0.045). Conclusions: Either spontaneous or induced abortion alone was associated with an increased risk of premature mortality, with induced abortion alone particularly linked to cardiovascular death. Future studies are encouraged to explore the underlying mechanisms.

Unraveling the influence of CRISPR/Cas13a reaction components on enhancing trans-cleavage activity for ultrasensitive on-chip RNA detection.

The CRISPR/Cas13 nucleases have been widely documented for nucleic acid detection. Understanding the intricacies of CRISPR/Cas13's reaction components is pivotal for harnessing its full potential for biosensing applications. Herein, we report on the influence of CRISPR/Cas13a reaction components on its trans-cleavage activity and the development of an on-chip total internal reflection fluorescence microscopy (TIRFM)-powered RNA sensing system. We used SARS-CoV-2 synthetic RNA and pseudovirus as a model system. Our results show that optimizing Mg2+ concentration, reporter length, and crRNA combination significantly improves the detection sensitivity. Under optimized conditions, we detected 100 fM unamplified SARS-CoV-2 synthetic RNA using a microtiter plate reader. To further improve sensitivity and provide a new amplification-free RNA sensing toolbox, we developed a TIRFM-based amplification-free RNA sensing system. We were able to detect RNA down to 100 aM. Furthermore, the TIRM-based detection system developed in this study is 1000-fold more sensitive than the off-coverslip assay. The possible clinical applicability of the system was demonstrated by detecting SARS-CoV-2 pseudovirus RNA. Our proposed sensing system has the potential to detect any target RNA with slight modifications to the existing setup, providing a universal RNA detection platform.

The Investigation of Neuromimetic Dynamics in Ferroelectrics via In Situ TEM.

The core task of neuromorphic devices is to effectively simulate the behavior of neurons and synapses. Based on the functionality of ferroelectric domains with the advantages of low power consumption and high-speed response, great progress has been made in realizing neuromimetic behaviors such as ferroelectric synaptic devices. However, the correlation between the ferroelectric domain dynamics and neuromimetic behavior remains unclear. Here, we reveal the correlation between domain/domain wall dynamics and neuromimetic behaviors from a microscopic perspective in real-time by using high temporal and spatial resolution in situ transmission electron microscopy. Furthermore, we propose utilizing ferroelectric microstructures for the simultaneous simulation of neuronal and synaptic plasticity, which is expected to improve the integration and performance of ferroelectric neuromorphic devices. We believe that this work to study neuromimetic behavior from the perspective of domain dynamics is instructive for the development of ferroelectric neuromorphic devices.

Evolutionary divergence of subgenomes in common carp provides insights into speciation and allopolyploid success.

Hybridization and polyploidization have made great contributions to speciation, heterosis, and agricultural production within plants, but there is still limited understanding and utilization in animals. Subgenome structure and expression reorganization and cooperation post hybridization and polyploidization are essential for speciation and allopolyploid success. However, the mechanisms have not yet been comprehensively assessed in animals. Here, we produced a high-fidelity reference genome sequence for common carp, a typical allotetraploid fish species cultured worldwide. This genome enabled in-depth analysis of the evolution of subgenome architecture and expression responses. Most genes were expressed with subgenome biases, with a trend of transition from the expression of subgenome A during the early stages to that of subgenome B during the late stages of embryonic development. While subgenome A evolved more rapidly, subgenome B contributed to a greater level of expression during development and under stressful conditions. Stable dominant patterns for homoeologous gene pairs both during development and under thermal stress suggest a potential fixed heterosis in the allotetraploid genome. Preferentially expressing either copy of a homoeologous gene at higher levels to confer development and response to stress indicates the dominant effect of heterosis. The plasticity of subgenomes and their shifting of dominant expression during early development, and in response to stressful conditions, provide novel insights into the molecular basis of the successful speciation, evolution, and heterosis of the allotetraploid common carp.

Identification of novel biomarker hsa_circ_0003914 for rheumatoid arthritis from plasma exosomes.

Rheumatoid arthritis (RA) is a complex autoimmune disease featuring invasive and infiltrative fibroblast-like synoviocytes (FLS) that lead to joint damage. While current RA pathological mechanisms remain incompletely defined, exosomes have been implicated as having the potential to drive disease progression due to their ability to deliver different types of biomolecules to tissues effected by RA. One potentially disease exacerbating molecule type found in exosomes are Circular RNAs (circRNAs), which are highly stable and have been previously implicated in RA pathogenesis. Here, we examine hsa_circ_0003914, a circRNA found in exosomes located in blood plasma, for a role in RA. Plasma exosomes were isolated and injected into collagen-induced arthritis (CIA) mice, followed by functional experiments to analyze the influence of exosomes on FLS formation. Sequencing revealed the presence of hsa_circ_0003914 in exosomes, so we examined its association with clinical markers in RA. Finally, the role for hsa_circ_0003914 in RA was directly confirmed through in vivo and in vitro experiments. We found that plasma exosomes isolated from RA patients could aggravate the disease of CIA mice, compared to exosomes isolated from healthy control patients. Hsa_circ_0003914 was highly enriched in the exosomes of RA patients. Mechanistically, Hsa_circ_0003914 promoted abnormal cell proliferation, migration, invasion and stimulated the secretion of inflammatory cytokines in FLSs through targeting NF-κB/p65 signaling pathway. Interestingly, knockdown of hsa_circ_0003914 rescued disease phenotypes in CIA mice. Taken together, these data implicate hsa_circ_0003914 as a potential therapeutic target for the prevention and management of RA.

The fusiform skin paddle in fibula free flap: a fusiform-designed skin paddle for maxillofacial soft defect reconstruction and reducing leg wound tension.

Objective: To investigate the feasibility of leg wound closure and reconstruction of maxillofacial soft defect by a fusiform-designed skin paddle in fibula free flap (FFF). Methods: Fifty patients who underwent FFF for reconstruction of maxillofacial soft defect were divided into two groups. The fusiform group (20 patients) was treated using a fusiform-designed skin paddle in FFF (skin paddle width less than 2 cm), and leg wound was closed using primary suturing. Reconstruction of the maxillofacial soft defect or filling of dead space was achieved by folding the fusiform skin paddle. The conventional group (30 patients) was treated using the conventional-designed skin paddle (skin paddle width no less than 2.5 cm). The leg wound was closed using mattress suturing or skin graft, while reconstruction of the maxillofacial soft defect or filling of dead space by conventional way. The average postoperative length of hospital stay, healing time of leg wound, and post-surgical complications were recorded at least 6 months after the surgery. Results: Compared with traditional method, the fusiform-designed skin paddle reduced the average healing time of the leg wound (fusiform group: 11.05 days, conventional group: 14.77 days, P < 0.05). The average length-to-width ratio in fusiform group was significantly greater than that of in conventional group (fusiform group: 5.85, conventional group: 2.93, P < 0.05), and no difference was observed on the graft size of skin paddle between two groups (fusiform group: 23.13, conventional group: 27.13, P > 0.05). The post-surgical early complications of the leg wound in the conventional group were higher than that of in the fusiform group (fusiform group: 0%, conventional group: 6.67%), while the post-surgical late complication of the donor site between the two groups showed no case. Healing disorders of maxillofacial soft reconstruction in the conventional group were higher than that of in the fusiform group (fusiform group: 5.26%, conventional group: 20.69%). Conclusions: Fusiform-designed skin paddle for closure of the leg wound and maxillofacial soft defect is a feasible alternative to the conventional- designed skin paddle. The fusiform- designed skin paddle resulted in the less postoperative length of hospital stay, shorter healing time of leg wound and less complication.

Revealing the structural evolution of CuAg composites during electrochemical carbon monoxide reduction.

Comprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.

Survival Analysis and Immune Differences of HIV Long-Term Non-progressors in Xinjiang China: A 12-Year Prospective Cohort Observation.

This 12-year cohort study of 80 long-term non-progressors (LTNPs) observed a cumulative follow-up duration of 628.5 person-years. Among them, 60 received antiretroviral therapy (ART) for a total of 418.6 person-years. Twenty-four deaths occurred during the follow-up period, with an average age of 42.36 years and a lowest 8-year survival rate of 0.90. Cox model analysis revealed that the risk of AIDS-related death was 1.47 times higher for non-marital, non-commercial heterosexual transmission than for injection drug use. Treatment initiation at ages 31-40 was correlated with an elevated risk of mortality, while treatment for 3-10 years reduced mortality risks in untreated LTNPs. Flow cytometry observed significant differences in the proportion of NK cells. Long-term ART (> 2 years) before LTNPs developed AIDS symptoms could lower mortality risk and potentially extend lifespan, especially when it was initiated at a younger age without affecting NK cell balance. Epidemiological and immunological studies on ART-treated LTNPs are vital for advancing HIV treatment and achieving functional cures for AIDS individuals.

RESUMEN: Este estudio de cohorte de 12 años con 80 no progresores a largo plazo (LTNPs) observó un total acumulado de 628.5 personas-año. De ellos, 60 recibieron terapia antirretroviral (TAR) durante un total de 418.6 personas-año. Se produjeron veinticuatro muertes durante el período del estudio, con una edad promedio de 42.36 años y una tasa de supervivencia más baja de 0.90 a los 8 años. El análisis del modelo de Cox identificó que la transmisión heterosexual no marital ni comercial presentaba un riesgo 1.47 veces mayor de muerte relacionada con el SIDA en comparación con el uso de drogas inyectables. Comenzar el tratamiento entre los 31-40 años mostró incrementos en los riesgos de mortalidad, mientras que 3-10 años de tratamiento redujeron los riesgos de mortalidad en LTNPs no tratados. Se observaron diferencias significativas en las proporciones de células NK desde el punto de vista inmunológico. La TAR a largo plazo (> 2 años) antes de la aparición de síntomas del SIDA en LTNPs podría disminuir el riesgo de mortalidad y potencialmente prolongar la vida, especialmente si se inicia a una edad más temprana sin afectar el equilibrio de las células NK. Los estudios epidemiológicos e inmunológicos sobre LTNPs tratados con TAR son fundamentales para el progreso del tratamiento del VIH y la cura funcional del SIDA.

Alkali cation-induced cathodic corrosion in Cu electrocatalysts.

The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., -0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

On-mask detection of SARS-CoV-2 related substances by surface enhanced Raman scattering.

We have developed a convenient surface-enhanced Raman scattering (SERS) platform based on vertical standing gold nanowires (v-AuNWs) which enabled the on-mask detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related substances such as the Spike-1 protein and the corresponding pseudo-virus. The Spike-1 protein was clearly distinguished from BSA protein with an accuracy above 99 %, and the detection limit could be achieved down to 0.01 µg/mL. Notably, a similar accuracy was achieved for the pseudo-SARS-CoV-2 (pSARS-2) virus as compared to the pseudo-influenza H7N9 (pH7N9) virus. The sensing strategy and setups could be easily adapted to the real SARS-CoV-2 virus and other highly contagious viruses. It provided a promising way to screen the virus carriers by a fast evaluation of their wearing v-AuNWs integrated face-mask which was mandatory during the pandemic.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

The UF-5000 Atyp.C parameter is an independent risk factor for bladder cancer.

Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The "Atyp.C" parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case-control study identified clinical primary or newly recurrent BC (study period, 2022-2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman's rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P < 0.001). Urinary Atyp.C values were positively correlated with BC pathological grade and invasion (r = 0.360, P < 0.001; r = 0.367, P < 0.001). Urinary Atyp.C was an independent risk factor for BC and closely related with BC pathological grade and invasion. Elevated urinary Atyp.C values was an independent risk factor for BC. Our findings support the use of Atyp.C as a marker that will potentially aid in the early diagnosis and long-term surveillance of new and recurrent BC cases.

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Effectiveness of the acute stroke care map program in reducing in-hospital delay for acute ischemic stroke in a Chinese urban area: an interrupted time series analysis.

Background: Timely intravenous thrombolysis (IVT) is crucial for improving outcomes in acute ischemic stroke (AIS) patients. This study evaluates the effectiveness of the Acute Stroke Care Map (ASCaM) initiative in Shenyang, aimed at reducing door-to-needle times (DNT) and thus improving the timeliness of care for AIS patients. Methods: An retrospective cohort study was conducted from April 2019 to December 2021 in 30 hospitals participating in the ASCaM initiative in Shenyang. The ASCaM bundle included strategies such as EMS prenotification, rapid stroke triage, on-call stroke neurologists, immediate neuroimaging interpretation, and the innovative Pre-hospital Emergency Call and Location Identification feature. An interrupted time series analysis (ITSA) was used to assess the impact of ASCaM on DNT, comparing 9 months pre-intervention with 24 months post-intervention. Results: Data from 9,680 IVT-treated ischemic stroke patients were analyzed, including 2,401 in the pre-intervention phase and 7,279 post-intervention. The ITSA revealed a significant reduction in monthly DNT by -1.12 min and a level change of -5.727 min post-ASCaM implementation. Conclusion: The ASCaM initiative significantly reduced in-hospital delays for AIS patients, demonstrating its effectiveness as a comprehensive stroke care improvement strategy in urban settings. These findings highlight the potential of coordinated care interventions to enhance timely access to reperfusion therapies and overall stroke prognosis.

Chemokines and lymphocyte homing in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that typically presents with lymphocyte, dendritic cell, and macrophage infiltration of exocrine gland ducts and the formation of ectopic germinal centers. The interactions of lymphocyte homing receptors and addressins and chemokines and their receptors, such as α4ß7/MAdCAM-1, LFA-1/ICAM-1, CXCL13/CXCR5, CCL25/CCR9, CX3CL1/CX3CR1, play important roles in the migration of inflammatory cells to the focal glands and the promotion of ectopic germinal center formation in SS. A variety of molecules have been shown to be involved in lymphocyte homing, including tumor necrosis factor-α, interferon (IFN)-α, IFN-ß, and B cell activating factor. This process mainly involves the Janus kinase-signal transducer and activator of transcription signaling pathway, lymphotoxin-ß receptor pathway, and nuclear factor-κB signaling pathway. These findings have led to the development of antibodies to cell adhesion molecules, antagonists of chemokines and their receptors, compounds interfering with chemokine receptor signaling, and gene therapies targeting chemokines and their receptors, providing new targets for the treatment of SS in humans. The aim of this study was to explore the relationship between lymphocyte homing and the pathogenesis of SS, and to provide a review of recent studies addressing lymphocyte homing in targeted therapy for SS.

Leisure-time physical activity is associated with depressive symptoms in cancer patients: Data from the NHANES 2007-2018.

BACKGROUND: Cancer patients have a higher risk of depression and are associated with severe adverse prognosis. The relationship between leisure-time physical activity (LTPA) and depressive symptoms in cancer patients is currently unclear. Therefore, our study mainly explores the potential association between LTPA and the weekly cumulative time of LTPA with depressive symptoms in cancer patients. METHODS: We included and analyzed 3368 cancer patients (aged >20 years) from the National Health and Nutrition Examination Survey (NHANES) of the United States from 1999 to 2018. The LTPA score was evaluated through a self-report questionnaire, while depressive symptoms were evaluated through the Health Questionnaire-9 (PHQ-9). Multiple logistic regression analysis was used to explore the relationship between LTPA duration and the occurrence of cancer-related depressiive symptoms. Linear correlation was studied using the restricted cubic spline method. RESULTS: According to a fully adjusted multivariate logistic regression model with confounding variables, the odds ratio (OR) between LTPA and depressive symptoms in cancer patients in this study was 0.59 (95 % confidence interval = 0.39, 0.92; P = 0.02). When the LTPA level was ≥300 min/week, the incidence of depressive symptoms was reduced by 59 % (OR = 0.41, 95 % CI = 0.21, 0.83). In addition, the cubic spline method was used to obtain a linear negative correlation between LTPA duration and tumor depressive symptoms. CONCLUSION: LTPA was negatively correlated with cancer-related depressive symptoms, and the cumulative time of LTPA/week was linearly correlated with depressive symptoms. The slope of the benefit curve changed significantly when the cumulative time of LTPA reached 600 min per week, suggesting that appropriately increasing LTPA had significant benefits on mental health of cancer patients.