Neurophysiological Characteristics in Type II and Type III 5q Spinal Muscular Atrophy Patients: Impact of Nusinersen Treatment.

Objective: This study aimed to observe the neurophysiological characteristics of type II and type III 5q spinal muscular atrophy (SMA) patients and the changes in peripheral motor nerve electrophysiology after Nusinersen treatment, as well as the influencing factors. Methods: This single-center retrospective case-control study collected clinical data and peripheral motor nerve CMAP parameters from 42 5qSMA patients and 42 healthy controls at the Second Affiliated Hospital of Xi'an Jiaotong University (January 2021 to December 2022). It evaluated changes in motor function and CMAP amplitude before and after Nusinersen treatment. Results: Our investigation encompassed all symptomatic and genetically confirmed SMA patients, consisting of 32 type II and 10 type III cases, with a median age of 57 months (29.5 to 96 months). Comparative analysis with healthy controls revealed substantial reductions in CMAP amplitudes across various nerves in both type II and type III patients. Despite the administration of Nusinersen treatment for 6 or 14 months to the entire cohort, discernible alterations in motor nerve amplitudes were not observed, except for a significant improvement in younger patients (≤36 months) at the 14-month mark. Further scrutiny within the type II subgroup unveiled that individuals with a disease duration ≤12 months experienced a noteworthy upswing in femoral nerve amplitude, a statistically significant difference when compared to those with >12 months of disease duration. Conclusion: Motor nerve amplitudes were significantly decreased in type II and type III 5q SMA patients compared to healthy controls. Nusinersen treatment showed better improvement in motor nerve amplitudes in younger age groups and those with shorter disease duration, indicating a treatment-time dependence.

Electrical impedance tomography as a bedside assessment tool for COPD treatment during hospitalization.

For patients with chronic obstructive pulmonary disease (COPD), the assessment of the treatment efficacy during hospitalization is of importance to the optimization of clinical treatments. Conventional spirometry might not be sensitive enough to capture the regional lung function development. The study aimed to evaluate the feasibility of using electrical impedance tomography (EIT) as an objective bedside evaluation tool for the treatment of acute exacerbation of COPD (AECOPD). Consecutive patients who required hospitalization due to AECOPD were included prospectively. EIT measurements were conducted at the time of admission and before the discharge simultaneously when a forced vital capacity maneuver was conducted. EIT-based heterogeneity measures of regional lung function were calculated based on the impedance changes over time. Surveys for attending doctors and patients were designed to evaluate the ease of use, feasibility, and overall satisfaction level to understand the acceptability of EIT measurements. Patient-reported outcome assessments were conducted. User's acceptance of EIT technology was investigated with a five-dimension survey. A total of 32 patients were included, and 8 patients were excluded due to the FVC maneuver not meeting the ATS criteria. Spirometry-based lung function was improved during hospitalization but not significantly different (FEV1 %pred.: 35.8% ± 6.7% vs. 45.3% ± 8.8% at admission vs. discharge; p = 0.11. FVC %pred.: 67.8% ± 0.4% vs. 82.6% ± 5.0%; p = 0.15. FEV1/FVC: 0.41 ± 0.09 vs. 0.42 ± 0.07, p = 0.71). The symptoms of COPD were significantly improved, but the correlations between the improvement of symptoms and spirometry FEV1 and FEV1/FVC were low (R = 0.1 and -0.01, respectively). The differences in blood gasses and blood tests were insignificant. All but one EIT-based regional lung function parameter were significantly improved after hospitalization. The results highly correlated with the patient-reported outcome assessment (R > 0.6, p < 0.001). The overall acceptability score of EIT measurement for both attending physicians and patients was high (4.1 ± 0.8 for physicians, 4.5 ± 0.5 for patients out of 5). These results demonstrated that it was feasible and acceptable to use EIT as an objective bedside evaluation tool for COPD treatment efficacy.

[Clinical features of congenitally enlarged bony portion of Eustachian tube].

Objective:To investigate the clinical features of patients with congenitally enlarged bony portions of the Eustachian tube（ET）. Methods:The medical history, physical examination, hearing test, temporal bone high resolution computed tomography（HRCT） of six patients（nine ears） with congenitally enlarged bony portion of the ET were retrospectively analyzed. Results:Four patients were men and two were women. The minimum, maximum, and average ages were 5, 21, and（14.7±6.4） years, respectively. Three malformations were bilateral and three were left-sided. Three ears had conductive hearing loss（average bone and air conduction thresholds were 13.7 dB and 71.3 dB）, three had mixed hearing loss（average bone and air conduction thresholds were 27.7 dB and 83.7 dB）, and one had extremely severe sensorineural hearing loss. The average maximum length and width of the enlarged bony ET on temporal bone HRCT were（22.61±2.94） mm and（6.50±2.33） mm, respectively. The enlargement was combined with an external auditory canal malformation in six ears, narrow tympanic cavity in six, tympanic antrum malformation in five, ossicular chain malformation in seven, cochlear malformation in six, helicotrema malformation in three, vestibule widening in two, semicircular canal malformation in three, vestibular window malformation in six, facial nerve abnormality in five, internal auditory meatus malformation in two, low middle cranial fossa in eight, and severe internal carotid artery malformation in one. Conclusion:Bony ET enlargement is a rare congenital middle ear malformation which could combined with other ear malformations. Patients can have no ET dysfunction but different patterns of hearing loss. The defect is usually found unintentionally during imaging, and the HRCT of temporal bone is significant.

Recent progress and outlooks in rhodamine-based fluorescent probes for detection and imaging of reactive oxygen, nitrogen, and sulfur species.

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.

High-sensitivity dual U-shaped PCF-SPR refractive index sensor for the detection of gas and liquid analytes.

A dual U-shaped photonic crystal fiber (PCF) biochemical sensor based on surface plasmon resonance (SPR) is designed for the simultaneous detection of gas and liquid analytes, and the properties are analyzed by the full vector finite element method (FEM). SPR is excited by placing gold nanowires on the inner surface of the U-shaped device. In this technique, the traditional metal deposition process can be replaced, subsequently reducing the difficulty and complexity of actual production and improving the phase matching between the basic mode and plasmonic modes. To improve the detection properties, the structural parameters of the sensor including the air hole diameter, spacing, gold nanowire diameter, and polishing depth are optimized, and to better evaluate and analyze the sensing properties, the wavelength and amplitude modulation inquiry method is adopted. The results show that the maximum wavelength sensitivity (WS), amplitude sensitivity (AS), minimum resolution (R), and optimal FOM are 35,000 nm/RIU, 438.08R I U -1, 2.86×10-6 R I U, and 165.16R I U -1, respectively. In addition, the sensor can detect analyte RIs between 1.00 and 1.36 for gas and liquid analytes simultaneously. Owing to the simple structure, low cost, and ambient-condition monitoring, the sensor has large potential in a myriad of applications including sewage treatment, food safety, humoral regulation, environmental and biological monitoring, and medical diagnosis.

COVID-19 vaccination uptake in children with epilepsy and vaccine hesitancy among their parents: a survey.

This study explored the coronavirus disease 2019 (COVID-19) vaccination coverage among children with epilepsy (CwE), factors affecting vaccination coverage, and the effect of COVID-19 vaccines on epilepsy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A questionnaire was administered to CwE and their parents at the Pediatric Neurology Clinic of the Second Affiliated Hospital of Xi'an Jiaotong University between December 12, 2022, and February 28, 2023. Data were analyzed using the t-tests, chi-square tests, and logistic regression. The analysis included 250 CwE who responded to the survey; of these, 152 (60.8%) had been vaccinated against COVID-19. COVID-19 vaccine hesitancy in parents whose CwE were not vaccinated was mostly due to concerns of vaccine-related exacerbation of seizures and of vaccine-related adverse reactions (44.30% and 41.90% of the respondents, respectively). Univariate analysis showed that vaccination and number of doses of vaccine did not affect seizure incidence within 1 month of SARS-CoV-2 infection. Logistic regression analysis showed that CwE below primary school age, and those taking two or more antiseizure medication (ASMs) were less likely to be vaccinated (p = 0.007).   Conclusion: The primary reasons for vaccine hesitancy among parents of unvaccinated CwE were concerns regarding seizure exacerbation and adverse reactions following COVID-19 vaccination. CwE who were below primary school age and those who took two or more ASMs were less likely to be vaccinated. Addressing parents' concerns is necessary to build their confidence in COVID-19 vaccines and ensure that CwE are vaccinated. What is Known: • People with epilepsy have a higher risk of severe and fatal COVID-19 than those without epilepsy but, despite this, COVID-19 vaccination coverage is considerably lower in people with epilepsy than in people without epilepsy. What is New: • In unvaccinated children with epilepsy, the foremost reasons for COVID-19 vaccine hesitancy among parents were concerns about seizure exacerbation and vaccine-related adverse reactions. • Vaccination and number of doses of vaccine did not exacerbate seizures in children with epilepsy, those below primary school level and those taking two or more antiseizure medications were less likely to be vaccinated.

Prevalence and Cancer-Specific Patterns of Functional Disability Among US Cancer Survivors, 2017-2022.

PURPOSE: To examine the prevalence and cancer-specific patterns of functional disabilities among US cancer survivors. METHODS: Data from 47,768 cancer survivors and 2,432,754 noncancer adults age 18 years and older from the 2017 to 2022 Behavioral Risk Factor Surveillance System were analyzed. Functional disabilities assessed included mobility disability (ie, serious difficulty walking or climbing stairs) and self-care disability (ie, self-reported difficulty dressing or bathing). Multivariable logistic regression models were used to assess the associations between functional disabilities and sociodemographic, lifestyle, and health-related factors. RESULTS: Cancer survivors tended to be older and non-Hispanic White than noncancer adults. The prevalence of mobility disability (27.9% v 13.4%) and self-care disability (7.4% v 3.8%) were higher among cancer survivors compared with noncancer adults. After multivariable adjustments, cancer survivors were more likely to report mobility (odds ratio [OR], 1.21 [95% CI, 1.16 to 1.26]) and self-care (OR, 1.19 [95% CI, 1.10 to 1.29]) disability than noncancer adults. The prevalence of mobility (34.9% v 26.3%) and self-care disability (9.8% v 6.7%) was higher in cancer survivors who were receiving active cancer treatment than in those who had completed cancer treatment. Higher prevalence of mobility and self-care disabilities was observed in cancer survivors who were racial/ethnic minorities and with higher BMI, low physical activity, lower levels of education and/or income, comorbidities, and those experiencing cancer/treatment-related pain. Patterns of mobility and self-care disabilities varied across cancer types. CONCLUSION: Over a quarter of US cancer survivors reported mobility disability, and nearly 10% reported self-care disability, with patterns varying across cancer types and treatment status. Racial/ethnic minorities, along with underserved groups and individuals with unhealthy lifestyles or comorbidities, were notably more affected by functional disabilities, underscoring the need for targeted disability prevention efforts.

Status of mental and social activities of young and middle-aged patients after papillary thyroid cancer surgery.

Background: Papillary thyroid cancer (PTC) is prevalent among younger populations and has a favorable survival rate. However, a significant number of patients experience psychosocial stress and a reduced quality of life (QoL) after surgical treatment. Therefore, comprehensive evaluations of the patients are essential to improve their recovery. Methods: The present study enrolled 512 young and middle-aged patients diagnosed with PTC who underwent surgery at our institution between September 2020 and August 2021. Each participant completed a series of questionnaires: Generalized Anxiety Disorder 7 (GAD-7), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Thyroid Cancer-Specific Quality of Life Questionnaire (THYCA-QoL), and Readiness to Return-to-Work Scale (RRTW). Results: GAD-7 data showed that almost half of the study subjects were experiencing anxiety. Regarding health-related quality of life (HRQoL), participants reported the highest levels of fatigue, insomnia, voice problems, and scarring, with patients in anxious states reporting worse symptoms. Based on RRTW, more than half of the subjects had returned to work and had better HRQoL compared to the others who were evaluating a possible return to work. Age, gender, BMI, education, diet, residence, health insurance, months since surgery, monthly income, and caregiver status were significantly correlated with return to work. Additionally, having a caregiver, higher monthly income, more time since surgery, and living in a city or village were positively associated with return to work. Conclusion: Young and middle-aged patients with PTC commonly experience a range of health-related issues and disease-specific symptoms following surgery, accompanied by inferior psychological well-being, HRQoL, and work readiness. It is crucial to prioritize timely interventions targeting postoperative psychological support, HRQoL improvement, and the restoration of working ability in PTC patients.

Con7 is a key transcription regulator for conidiogenesis in the plant pathogenic fungus Fusarium graminearum.

The mycelium of the plant pathogenic fungus Fusarium graminearum exhibits distinct structures for vegetative growth, asexual sporulation, sexual development, virulence, and chlamydospore formation. These structures are vital for the survival and pathogenicity of the fungus, necessitating precise regulation based on environmental cues. Initially identified in Magnaporthe oryzae, the transcription factor Con7p regulates conidiation and infection-related morphogenesis, but not vegetative growth. We characterized the Con7p ortholog FgCon7, and deletion of FgCON7 resulted in severe defects in conidium production, virulence, sexual development, and vegetative growth. The mycelia of the deletion mutant transformed into chlamydospore-like structures with high chitin level accumulation. Notably, boosting FgABAA expression partially alleviated developmental issues in the FgCON7 deletion mutant. Chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) analysis confirmed a direct genetic link between FgABAA and FgCON7. Furthermore, the chitin synthase gene Fg6550 (FGSG_06550) showed significant upregulation in the FgCON7 deletion mutant, and altering FgCON7 expression affected cell wall integrity. Further research will focus on understanding the behavior of the chitin synthase gene and its regulation by FgCon7 in F. graminearum. This study contributes significantly to our understanding of the genetic pathways that regulate hyphal differentiation and conidiation in this plant pathogenic fungus. IMPORTANCE: The ascomycete fungus Fusarium graminearum is the primary cause of head blight disease in wheat and barley, as well as ear and stalk rot in maize. Given the importance of conidia and ascospores in the disease cycle of F. graminearum, precise spatiotemporal regulation of these biological processes is crucial. In this study, we characterized the Magnaporthe oryzae Con7p ortholog and discovered that FgCon7 significantly influences various crucial aspects of fungal development and pathogenicity. Notably, overexpression of FgABAA partially restored developmental defects in the FgCON7 deletion mutant. ChIP-qPCR analysis confirmed a direct genetic link between FgABAA and FgCON7. Furthermore, our research revealed a clear correlation between FgCon7 and chitin accumulation and the expression of chitin synthase genes. These findings offer valuable insights into the genetic mechanisms regulating conidiation and the significance of mycelial differentiation in this plant pathogenic fungus.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Kai-xin-san improves cognitive impairment in D-gal and Aß25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood. AIM OF THE STUDY: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota. MATERIALS AND METHODS: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aß25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments. RESULTS: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant. CONCLUSION: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

[Acute heart failure in a neonate]. / æ–°ç”Ÿå„¿æ€¥æ€§å¿ƒåŠŸèƒ½ä¸å ¨1例.

The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.

Naringenin alleviates liver fibrosis by triggering autophagy-dependent ferroptosis in hepatic stellate cells.

Inhibition of activated hepatic stellate cells (HSCs) is a promising approach for treating liver fibrosis, and the ferroptosis has emerged as a pivotal mechanism to achieve this inhibition. The effects of naringenin, a flavonoid with anti-inflammatory properties, have not been thoroughly examined in liver fibrosis. Therefore, we used cholestasis model to study the effect of naringenin on liver fibrosis. Our findings demonstrated a significant exacerbation of liver tissue damage and fibrosis in mice subjected to bile duct ligation (BDL), accompanied by a substantial upregulation of fibrogenesis-related gene expression. Notably, naringenin administration markedly alleviated liver injury and fibrosis in these mice. Furthermore, naringenin exhibited inhibitory effects on the activation of HSCs, concurrently inducing ferroptosis. Importantly, naringenin significantly increased autophagic activity in HSCs. This effect was counteracted by co-administration of the autophagy inhibitor 3-MA, leading to a notable reduction in naringenin-induced HSC ferroptosis. In BDL model mice, naringenin demonstrated a mitigating effect on liver fibrosis, suggesting a potential correlation with naringenin-induced ferroptosis of HSCs. These results provide novel insights into the molecular mechanisms of naringenin-induced ferroptosis and highlight autophagy-dependent ferroptosis as a promising therapeutic strategy for liver fibrosis.

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer.

BACKGROUND: Treatment options for patients with gastric cancer (GC) continue to improve, but the overall prognosis is poor. The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present, and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups. AIM: To determined the effects of differentially expressed immune-related genes (DEIRGs) on the development, prognosis, tumor microenvironment (TME), and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations. METHODS: Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas (TCGA), and immune-related genes (IRGs) were searched from ImmPort. DEIRGs were extracted from the intersection of the differentially-expressed genes (DEGs) and IRGs lists. The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes (KEGGs) and Gene Ontology (GO) databases. To identify genes associated with prognosis, a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression. The tumor risk score was divided into high- and low-risk groups. The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model. The infiltration of immune cells was obtained using 'CIBERSORT,' and the infiltration of immune subgroups in high- and low-risk groups was analyzed. The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed. RESULTS: We collected 412 GC and 36 adjacent tissue samples, and identified 3627 DEGs and 1311 IRGs. A total of 482 DEIRGs were obtained. GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes, receptor ligand activity, and signaling receptor activators. KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors, neuroactive ligand receptor interactions, and viral protein interactions. We ultimately obtained an immune-related signature based on 10 genes, including 9 risk genes (LCN1, LEAP2, TMSB15A mRNA, DEFB126, PI15, IGHD3-16, IGLV3-22, CGB5, and GLP2R) and 1 protective gene (LGR6). Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, and risk curves confirmed that the risk model had good predictive ability. Multivariate COX analysis showed that age, stage, and risk score were independent prognostic factors for patients with GC. Meanwhile, patients in the low-risk group had higher tumor mutation burden and immunophenotype, which can be used to predict the immune checkpoint inhibitor response. Both cytotoxic T lymphocyte antigen4+ and programmed death 1+ patients with lower risk scores were more sensitive to immunotherapy. CONCLUSION: In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME. By providing risk factor analysis and prognostic information, our risk model can provide new directions for immunotherapy in GC patients.

Understanding the Cathode-Electrolyte Interfacial Chemistry in Rechargeable Magnesium Batteries.

Rechargeable magnesium batteries (RMBs) have garnered significant attention due to their potential to provide high energy density, utilize earth-abundant raw materials, and employ metal anode safely. Currently, the lack of applicable cathode materials has become one of the bottleneck issues for fully exploiting the technological advantages of RMBs. Recent studies on Mg cathodes reveal divergent storage performance depending on the electrolyte formulation, posing interfacial issues as a previously overlooked challenge. This minireview begins with an introduction of representative cathode-electrolyte interfacial phenomena in RMBs, elaborating on the unique solvation behavior of Mg2+, which lays the foundation for interfacial chemistries. It is followed by presenting recently developed strategies targeting the promotion of Mg2+ desolvation in the electrolyte and alternative cointercalation approaches to circumvent the desolvation step. In addition, efforts to enhance the cathode-electrolyte compatibility via electrolyte development and interfacial engineering are highlighted. Based on the abovementioned discussions, this minireview finally puts forward perspectives and challenges on the establishment of a stable interface and fast interfacial chemistry for RMBs.

Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma.

BACKGROUND: Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. RESULTS: The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. CONCLUSIONS: Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.

Characterization of Potting Epoxy Resins Performance Parameters Based on a Viscoelastic Constitutive Model.

To describe the evolution of residual stresses in epoxy resin during the curing process, a more detailed characterization of its viscoelastic properties is necessary. In this study, we have devised a simplified apparatus for assessing the viscoelastic properties of epoxy resin. This apparatus employs a confining cylinder to restrict the circumferential and radial deformations of the material. Following the application of load by the testing machine, the epoxy resin sample gradually reduces the gap between its surface and the inner wall of the confining cylinder, ultimately achieving full contact and establishing a continuous interface. By recording the circumferential stress-strain on the outer surface of the confining cylinder, we can deduce the variations in material bulk and shear moduli with time. This characterization spans eight temperature points surrounding the glass transition temperature, revealing the bulk and shear relaxation moduli of the epoxy resin. Throughout the experiments, the epoxy resin's viscoelastic response demonstrated a pronounced time-temperature dependency. Below the glass transition temperature, the stress relaxation response progressively accelerated with increasing temperature, while beyond the glass transition temperature, the stress relaxation time underwent a substantial reduction. By applying the time-temperature superposition principle, it is possible to construct the relaxation master curves for the bulk and shear moduli of the epoxy resin. By fitting the data, we can obtain expressions for the constitutive model describing the viscoelastic behavior of the epoxy resin. In order to validate the reliability of the test results, a uniaxial tensile relaxation test was conducted on the epoxy resin casting body. The results show good agreement between the obtained uniaxial relaxation modulus curves and those derived from the bulk and shear relaxation modulus equations, confirming the validity of both the device design and the testing methodology.

Impact of the Pre-Dehydration and Drying Methods on the Mass Transfer and Quality Attributes of Yak Milk Casein.

Drying is an important preservation method of casein. Traditional natural draining and drying processes have low efficiency, long processing time, and poor product quality, which urgently need to be improved. This study investigated the effects of pre-dehydration intensities (30 N 30 min (PreD1) and 50 N 30 min (PreD2)) and drying methods (including pulsed vacuum drying (PVD), infrared drying (IRD), and hot air drying (HAD)) on the drying kinetics, drying modeling, and quality of yak milk casein. These findings reveal that PreD2 and PVD both had a positive impact on shortening the drying time. Compared to other combined treatments, PreD2-PVD had the shortest drying time of 6 h. The Midilli-Kucuk mathematical model effectively predicted the drying of casein. The yak milk casein powder treated with PreD2-PVD possessed a higher content of gross compositions, superior color, lower levels of fat oxidation and 5-hydroxymethylfurfural (5-HMF), and higher emulsifying activity index (EAI) and emulsion stability index (ESI) values. Overall, combining pre-dehydration with PVD proved effective in improving the drying rate and maintaining a good quality of yak milk casein, showing promising potential for industrial applications.

Metabolomics of cerebrospinal fluid reveals candidate diagnostic biomarkers to distinguish between spinal muscular atrophy type II and type III.

AIMS: Classification of spinal muscular atrophy (SMA) is associated with the clinical prognosis; however, objective classification markers are scarce. This study aimed to identify metabolic markers in the cerebrospinal fluid (CSF) of children with SMA types II and III. METHODS: CSF samples were collected from 40 patients with SMA (27 with type II and 13 with type III) and analyzed for metabolites. RESULTS: We identified 135 metabolites associated with SMA types II and III. These were associated with lysine degradation and arginine, proline, and tyrosine metabolism. We identified seven metabolites associated with the Hammersmith Functional Motor Scale: 4-chlorophenylacetic acid, adb-chminaca,(+/-)-, dodecyl benzenesulfonic acid, norethindrone acetate, 4-(undecan-5-yl) benzene-1-sulfonic acid, dihydromaleimide beta-d-glucoside, and cinobufagin. Potential typing biomarkers, N-cyclohexylformamide, cinobufagin, cotinine glucuronide, N-myristoyl arginine, 4-chlorophenylacetic acid, geranic acid, 4-(undecan-5-yl) benzene, and 7,8-diamino pelargonate, showed good predictive performance. Among these, N-myristoyl arginine was unaffected by the gene phenotype. CONCLUSION: This study identified metabolic markers are promising candidate prognostic factors for SMA. We also identified the metabolic pathways associated with the severity of SMA. These assessments can help predict the outcomes of screening SMA classification biomarkers.

A new species of Populus and the extensive hybrid speciation arising from it on the Qinghai-Tibet Plateau.

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.