Pro-Inflammatory Signaling Cascade Markers, Oxidative Stress-Inflammatory Signaling Axis, and Chronic Total Occlusion of Tibial Artery in Elderly Patients Suffering from Occlusion of Coronary Arteries.

INTRODUCTION: Oxidative response is a risk factor in the progression of arterial atherosclerosis. OBJECTIVE: This research study aimed to examine the effects of oxidative response on atherosclerotic susceptibility as well as the development of arteriosclerosis occlusions of the tibial artery through pro-inflammatory mediator genes in elderly patients with occlusion of coronary arteries. METHODS: We determined that oxidative stress biomarkers (Malondialdehyde-modified Low-density Lipoprotein (MDA-LDL), Oxidized Low-density Lipoprotein (Ox-LDL) as well as Heme Oxygenase- 1 (HO-1)] and the expressions of pro-inflammatory mediator genes [Toll-like Receptor 4 (TLR4), Nuclear Factor kappa-B (NF-κB), Myeloid Differentiating factor 88 (MyD88) and Growth Arrest-specific gene 6 (GAS6)] have an impact on the severity of arteriosclerosis occlusions of tibial artery in elderly patients suffering from occlusion of coronary arteries. RESULTS: Levels of MDA-LDL, Ox-LDL, HO-1, TLR4, NF-κB, MyD88, and GAS6 were increased in the occlusion of tibial arteries + two-vessel coronary occlusion group compared to the CON group and occlusion of tibial arteries + one-vessel coronary occlusion group, respectively (p < 0.001); they were also elevated in occlusion of tibial arteries + multiple-vessel coronary occlusion group compared to occlusion of tibial arteries + one-vessel coronary occlusion group and occlusion of tibial arteries + two-vessel coronary occlusion group, respectively (P < 0.001). This has indicated the key roles of oxidative stress and pro-inflammatory mediator genes in arteriosclerosis occlusions of tibial artery in elderly patients with occlusion of coronary arteries. CONCLUSION: Oxidative response may promote the expressions of inflammatory genes and enhance susceptibility to arteriosclerosis occlusions of the tibial artery in elderly patients with chronic total coronary occlusions.

Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study.

INTRODUCTION: Previous studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCOS. MATERIAL AND METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis. Datasets were from the largest published meta-analysis on gut microbiota composition and the FinnGen cohort of the IEU Open Genome-Wide Association Study Project database. Inverse variance weighted (IVW), MR-Egger, constrained maximum likelihood-based Mendelian randomization, weighted median, weighted mode, and simple mode were used. Cochran's Q and MR-Egger intercept tests were employed to measure the heterogeneity. RESULTS: A total of 211 gut microbiota taxa were identified in MR analysis. Nine taxa of bacteria, including Alphaproteobacteria (0.55, 0.30-0.99, p = 0.04), Bacilli (1.76, 1.07-2.91, p = 0.03), Bilophila (0.42, 0.23-0.77, p < 0.01), Blautia (0.16, 0.03-0.79, p = 0.02), Burkholderiales (2.37, 1.22-4.62, p = 0.01), Candidatus Soleaferrea (0.65, 0.43-0.98, p = 0.04), Cyanobacteria (0.51, 0.31-0.83, p = 0.01), Holdemania (0.53, 0.35-0.81, p < 0.01), and Lachnospiraceae (1.86, 1.04-3.35, p = 0.03), were found to be associated with PCOS in the above MR methods included at least IVW method. Cochran's Q statistics and MR-Egger intercept test suggested no significant heterogeneity. In addition, 69 taxa were shown significant for at least the IVW method in reverse MR analysis, of these, 25 had a positive correlation, and 37 had a negative correlation. Additionally, Alphaproteobacteria and Lachnospiraceae (0.95, 0.91-0.98, p < 0.01; 0.97, 0.94-0.99, p = 0.02, respectively) were shown a bidirected causally association with PCOS. CONCLUSIONS: Our study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.

Vegetation changes and influencing factors in different watersheds of Henan Province based on GEE and geographic detectors.

Clarifying vegetation changes and the driving factors can provide references for ecological restoration and sustainable social development. We analyzed vegetation distribution and trend changes in Henan Province and its basin zoning (Haihe River basin zoning, Yellow River basin zoning, Huaihe River basin zoning, Yangtze River basin zoning), with fractional vegetation cover data from 2000 to 2020 based on the Google Earth Engine platform, and by combining Theil-Sen Median trend analysis, Mann-Kendall test, and Hurst index. We also utilized factor detection and factor interaction to explore the individual and mutual influences of natural and anthropogenic factors on vegetation at different scales. The results showed that the fractional vegetation cover (FVC) in Henan Province exhibited a distribution pattern of higher coverage in the south and lower in the north during the study period, predominantly characterized by moderate to high vegetation coverage. The Yangtze River basin zoning had the highest coverage. FVC in Henan Province and its zoning exhibited a consistent pattern of fluctuating upward trends, with all areas showing significant improvement. Particularly, the Yangtze River basin zoning had the largest area of improvement. According to the Hurst index, apart from the possibility of continued improvement in the Huaihe River basin zoning, other zoning would be likely to shift from improvement to degradation in the future. Vegetation changes in Henan Province and its zoning were the result of combined effects of anthropogenic and natural factors, with the influence of these factors changing over time and the dominant factors varying by region. Anthropogenic factors such as land use/cover type and nighttime lighting had a stronger impact on vegetation than natural factors like elevation, slope, and annual mean low temperature. The interaction between factors, particularly between anthropogenic and natural factors, exhibited a nonlinear enhancing pattern.

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A comprehensive understanding of the evolution of soybean climate potential productivity and its response to climate change in Heilongjiang Province can offer reference and basis for further tapping soybean production potential and realizing stable and high yield of soybean in the frigid region. Based on meteorological data from 80 meteorological stations in Heilongjiang Province from 1961 to 2020, we estimated photosynthesis, light temperature, and climate potential productivity of soybean by the stepwise correction method, examined the spatiotemporal variations by spatial interpolation and statistical analysis methods, and analyzed the impact of changes in climate factors such as radiation, temperature, and precipitation on climate potential productivity. The results showed that during the study period, the average values of photosynthesis potential productivity (YQ), light-temperature potential productivity (YT), and climate potential productivity (YW) of soybean in Heilongjiang Province were 7533, 6444, and 3515 kg·hm-2, respectively. The temporal changes of those variables showed significant increasing trends, with increases of 125.9, 182.9, and 116.1 kg·hm-2·(10 a)-1, respectively. For the spatial distribution, YQ, YT, YW were characterized by high values in plains and lower in the mountains, and gradually decreased from southwest to northeast. Compared with that during 1961-1990, the high value zone of YW in period 1991-2020 expanded by 7.1%, and the low value zone decreased by 5.1%. YW showed a significant response to climate change. The potential temperature growth period was extended due to climate warming. The continuous increase in thermal resources, combined with relatively sufficient precipitation, effectively alleviated the negative impact of the decline in light resources on soybean production in Heilongjiang Province. The projected "warm and humid" climate would comprehensively boost climate potential productivity of soybean in Heilongjiang Province.

Time-dependent cardiovascular risks following pneumonia in inpatient and outpatient settings: A register-based cohort study.

Background: The elevated long-term cardiovascular disease (CVD) risks associated with pneumonia have been observed among inpatients, yet the risks associated with outpatients are less understood. Methods: We used register-based data and a matched cohort design, including 98,354 pneumonia inpatients and 44,486 outpatients, as well as a 5-fold number of matched healthy controls. Associations between pneumonia presentation (in inpatient and outpatient settings) and long-term CVD risks were measured by rate difference and hazard ratio (HR) using Poisson and Cox regressions in a time-dependent manner. Results: During a maximum follow-up period of 5.7 years of ischemic heart disease (IHD), heart failure (HF), and stroke were documented among pneumonia inpatients.Relative to healthy controls, pneumonia patients showed increased risks of IHD, HF, and stroke. Women and young inpatients demonstrated stronger associations of CVD with pneumonia; inpatients aged 60 years or older showed the highest excessive CVD risks. Conclusions: Pneumonia demanding outpatient and inpatient cares are intermediate-term and long-term risk factors of incident CVDs respectively, underscoring the need to plan setting-specific and time-dependent CVD-preventive cares following pneumonia presentation.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

In Vivo Thoracic Dorsal Root Ganglia (DRG) Calcium Imaging and ECG Recording for Studying Peripheral Nerve Stimulation.

The dorsal root ganglia (DRG), housing primary sensory neurons, transmit somatosensory and visceral afferent inputs to the dorsal horn of the spinal cord. They play a pivotal role in both physiological and pathological states, including neuropathic and visceral pain. In vivo calcium imaging of DRG enables real-time observation of calcium transients in single units or neuron ensembles. Accumulating evidence indicates that DRG neuronal activities induced by somatic stimulation significantly affect autonomic and visceral functions. While lumbar DRG calcium imaging has been extensively studied, thoracic segment DRG calcium imaging has been less explored due to surgical exposure and stereotaxic fixation challenges. Here, we utilized in vivo calcium imaging at the thoracic1 dorsal root ganglion (T1-DRG) to investigate changes in neuronal activity resulting from somatic stimulations of the forelimb. This approach is crucial for understanding the somato-cardiac reflex triggered by peripheral nerve stimulations (PENS), such as acupuncture. Notably, synchronization of cardiac function was observed and measured by electrocardiogram (ECG), with T-DRG neuronal activities, potentially establishing a novel paradigm for somato-visceral reflex in the thoracic segments.

Baicalein ameliorates chronic itch in ACD mice by suppressing the spinal astrocytic STAT3-LCN2 cascade.

Chronic itch is a maladaptive and debilitating symptom in patients with allergic contact dermatitis (ACD), adversely affecting their quality of life. There is a lack of effective treatments for ACD-associated uncontrollable itch. In this study, we explored the antipruritic effects of baicalein (BE), a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, and the underlying mechanisms in alleviating chronic itch triggered by diphenylcyclopropenone (DCP) in a mouse model of ACD. The ACD mice were intraperitoneally injected with BE (5, 30, and 60 mg·kg-1·d-1) for 7 days during the DCP challenge phase. The results showed that DCP-treated mice exhibited severe spontaneous scratching behaviors that was reduced after BE injections in a dose-dependent manner accompanied by inhibition of spinal astrocyte activation. We observed that the spinal astrocytic STAT3-LCN2 cascade plays a crucial role in controlling the activation of astrocytes in chronic itch. Intrathecal injection of the STAT3 inhibitor AG490 or Lcn2 siRNA significantly reduced scratching behavior and astrocyte activation in ACD mice. Moreover, BE markedly attenuated the increased phosphorylation of STAT3 (p-STAT3) and LCN2 expression in the spinal cords of ACD mice and in lipopolysaccharide-stimulated primary spinal astrocytes. Altogether, BE relieved chronic itch by suppressing the spinal astrocytic STAT3-LCN2 cascade. These findings provide a potential avenue for the management of chronic itch. Schematic summary of the main findings illustrating that BE alleviates chronic itch through suppressing the spinal astrocytic STAT3-LCN2 cascade. Specifically, BE suppresses the expression of p-STAT3 to inhibit the reactive state of astrocytes in spinal dorsal horn, and then decreases the expression of astrocytic LCN2 to alleviate chronic itch in ACD mice.

Mechanism of one-step hydrothermal nitric acid treatment for producing high adsorption capacity porous materials from coal gasification fine slag.

The increasing amount of coal gasification fine slag (CGFS) necessitates its resource utilization. CGFS, mainly composed of porous carbonaceous particles and partially fused spherical or agglomerated ash particles, is an inexpensive and high-quality raw material for preparing adsorbent materials. However, the challenge remains in developing a simple, low-cost, and environmentally friendly method to produce high-performance porous materials from CGFS. In this study, a one-step treatment method using 2 mol/L nitric acid under hydrothermal conditions was proposed for CGFS. The adsorbent material (CGFS-2 M) prepared under a solid-liquid ratio of 2:5 and an initial concentration of 200 mg/L methylene blue (MB) exhibited an equilibrium adsorption capacity as high as 210.20 mg/g. The excellent adsorption performance of CGFS-2 M can be attributed to several factors: acid leaching for mineral removal and pore formation, resulting in a specific surface area and total pore volume 2.2 and 1.6 times that of untreated CGFS, respectively, and an optimized mesoporous pore size distribution favorable for MB adsorption; optimal mineral removal and a well-defined carbon microcrystal structure providing more space for MB adsorption; nitric acid treatment increasing the surface oxygen content and hydrophilicity, enhancing its ability to remove MB. The synergistic effect of pore structure improvement and surface modification indicates a feasible research direction for enhancing the performance of CGFS-based adsorbent materials. These results provide theoretical support for the development of efficient CGFS-based adsorbents.

ROS exhaustion reverses the effects of hyperbaric oxygen on hemorrhagic transformation through reactivating microglia in post-stroke hyperglycemic mice.

Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-L-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

The current status and future trends of BET research in oncology.

Background: BET family proteins are important epigenetic and transcriptional regulators involved in the control of tumorigenesis and development and have become important targets for cancer therapy. However, there is no systematic bibliometric analysis in this field. A visual analysis of the research hotspots and trends of BET is helpful to understand the future development direction. Method: We used CiteSpace, VOSviewer, and Excel to visualize and analyze the trends regarding authors, journals, countries or regions, highly cited papers, and keywords in the field. Result: The results included a total of 946 publications. There are many more papers on BET proteins published since 2013. The papers are mainly from 44 countries, led by the U.S. and China. A total of 7381 authors were identified, among which Bradner, J.E. had the greatest number of articles and the greatest influence. Cancer Discovery was the journal with the most citations per article. Our analysis identified the most influential papers in the field, including highly cited papers and citation burst references. The most frequent keywords included 'expression', 'c-Myc', 'cancer', 'BRD4', 'BET inhibition', 'resistance', 'differentiation', and 'JQ1', which represent the focus of current and developing research fields. Conclusion: Research on BET is thriving. Collaboration and exchanges between countries and institutions must be strengthened in the future, and the mechanisms of BET-related pathways, the relationship between BET and various diseases, and the development of new BET inhibitors have become the major focus of current research and the trend of future research.

Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia.

BACKGROUND: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. METHODS: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. RESULTS: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. CONCLUSIONS: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

Motivators and barriers for studying podiatry in Australia and New Zealand: A mixed methods study.

BACKGROUND: Podiatry enrolments at Australian and New Zealand universities have decreased by 17.3% since 2015, which threatens the profession's sustainability and the health and wellbeing of Australian and New Zealand people and communities. Reasons for this decline remain unclear due to insufficient evidence on factors influencing career choices. The overarching aim of this study was to identify motivators and barriers for studying podiatry in Australia and New Zealand. METHODS: This study used a convergent mixed methods design. Students enrolled in (i) podiatry and (ii) relevant non-podiatry health, sport or science programs at nine Australian and one New Zealand university, were invited to participate in an online survey. First-year podiatry students were also invited to participate in an online workshop. Quantitative data were analysed using descriptive statistics and linear/logistic regression models. Three independent assessors used inductive thematic analysis for the qualitative data. RESULTS: Overall, 278 podiatry students (mean age 24.9 ± 8.5 years, 65.1% female) and 553 non-podiatry students (mean age 24.8 ± 8.2 years, 75.4% female; 32.2% from physiotherapy and 29.1% from occupational therapy) responded to the survey. Interest in a health-related career, wanting to make a difference to people's health, and opportunity to care for people from different backgrounds/age groups were key motivating factors among podiatry students. Barriers to studying podiatry were encountered by 28.1% of podiatry students. Thematic analysis identified seven themes concerning career choice, which are as follows: (i) awareness of profession and scope of practice; (ii) stereotypes and negative perceptions of the profession; (iii) awareness of career pathways; (iv) job prospects and earning potential; (v) working with people and building relationships; (vi) podiatry is not the first preference; and (vii) barriers which limit student enrolment. CONCLUSIONS: There are a variety of factors that motivate and influence students to study podiatry, however, altruistic reasons are most highly rated. Allied health students have limited understanding of the scope of practice and career opportunities in podiatry. Additionally, the podiatry profession often faces negative stereotypes. Further work is required to reverse the negative stereotypes and perceptions of podiatry and build knowledge of the profession's scope of practice, career pathways/opportunities, job prospects and earning potential.

Exploring the role of static magnetic field in supercooling storage from the viewpoint of meat quality and microbial community.

In order to explore the application prospects of static magnetic field (SMF) combined with supercooling in meat preservation, this study proposed a novel method of supercooling assisted by a stationary magnetic field (SMF + supercooling) for the preservation of chilled pork, evaluating its cooling rate and quality changes (e.g., water holding capacity, color, pH, and TVB-N), as well as the evolution trend of the microbiota. The results showed that SMF + supercooling significantly (P < 0.05) improved the cooling rate of pork. Compared to chilling and supercooling, SMF + supercooling significantly delayed the increase of TVB-N and TVC on the 12th day of storage (P < 0.05). SMF + supercooling treatment achieves the maintenance of pork water-holding capacity by inhibiting water migration, reducing drip loss, cooking loss, and centrifugal loss of pork. The 16S rDNA bacteria flora analysis demonstrated that SMF + supercooling treatment reduced the relative abundance of spoilage bacteria such as Acinetobacter, Streptococcus, and Pseudomonas, delaying the deterioration of pork quality caused by microbial growth. The SMF + supercooling treatment can be considered a novel refrigeration preservation method that delays the deterioration of pork quality and extends its shelf life.

Preparation and antifouling performance of tin-free self-polishing antifouling coatings based on side-chain suspended indole derivative structural resins.

Tin-free self-polishing antifouling coatings have the highest market share since organotin self-polishing antifouling coatings have been banned. However, its high dependence on cuprous oxide was found to have caused potential harm to the environment, making it necessary to improve the functionality of the resin. In this paper, a zinc acrylate resin with side chain hanging indole derivative structure was prepared by using N-(1H-5-bromoindole-3-methylene) (BIAM) with good biological activity as functional monomer. The functional resin with good antifouling performance was selected by antibacterial and algae inhibition experiments. The results showed that when the BIAM content was 9 %, the inhibition rates of the resin on E. coli and Prymnesium parvum reached 98 % and 90 %, respectively. Tin-free self-polishing antifouling coatings were prepared using the above resins as film-forming materials. The anti-protein adsorption performance and antifouling performance of the coating were tested by anti-protein adsorption experiment and real sea hanging plate experiment. The results showed that the coating containing indole derivative structure had good anti-protein adsorption performance and antifouling performance, and the higher the BIAM content, the better the anti-protein adsorption performance and marine antifouling performance.

Multifunctional and Ultrastable Co-MOF Effectively Separates Various Different Component Gas Mixtures.

Developing low-cost and multifunctional adsorbents for adsorption separation to obtain high-purity (>99.9%) gases is intriguing yet challenging. Notably, the ongoing trade-off between adsorption capacity and selectivity in separating multicomponent mixed gases still persists as a pressing scientific challenge requiring urgent attention. Herein, the ultrastable TJT-100 exhibits unique structural characteristics including uncoordinated carboxylate oxygen atoms, coordinated water molecules directed toward the pore surface, and sufficient Me2NH2+ cations in channels. TJT-100 exhibits a high adsorption capacity and exceptional separation performance, particularly notable for its high C2H2 capacity of 127.7 cm3/g and remarkable C2H2 selectivity over CO2 (5.4) and CH4 (19.8), which makes it a standout material for various separation applications. In a breakthrough experiment with a C2H2/CO2 mixture (v/v = 50/50), TJT-100 achieved a record-high C2H2 productivity of 69.33 L/kg with a purity of 99.9%. Additionally, TJT-100 demonstrates its effectiveness in separating CO2 from natural gas and flue gas. Its exceptional selectivity for CO2/CH4 (10.7) and CO2/N2 (11.9) results in a high CO2 productivity of 21.23 and 22.93 L/kg with 99.9% purity from CO2/CH4 (v/v = 50/50) and CO2/N2 (v/v = 15/85) mixtures, respectively.

Cathepsin C exacerbates EAE by promoting the expansion of Tfh cells and the formation of TLSs in the CNS.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) mediated by CD4+ T helper (Th) cells, and characterized by immune cell infiltration, demyelination and neurodegeneration, with no definitive cure available. Thus, it is pivotal and imperative to acquire more profound comprehension of the underlying mechanisms implicated in MS. Dysregulated immune responses are widely believed to play a primary role in the pathogenesis of MS. Recently, a plethora of studies have demonstrated the involvement of T follicular helper (Tfh) cells and tertiary lymphoid-like structures (TLSs) in the pathogenesis and progression of MS. Cathepsin C (CatC) is a cysteine exopeptidase which is crucial for the activation of immune-cell-associated serine proteinases in many inflammatory diseases in peripheral system, such as rheumatoid arthritis and septicemia. We have previously demonstrated that CatC is involved in neuroinflammation and exacerbates demyelination in both cuprizone-induced and experimental autoimmune encephalomyelitis (EAE) mouse models. However, the underlying immunopathological mechanism remains elusive. In the present study, we established a recombinant myelin oligodendrocyte glycoprotein 35-55 peptide-induced EAE model using conditional CatC overexpression mice to investigate the effects of CatC on the alteration of CD4+ Th subsets, including Th1, Th2, Th17, Tfh and T regulatory cells. Our findings demonstrated that CatC particularly enhanced the population of Tfh cell in the brain, resulting in the earlier onset and more severe chronic syndrome of EAE. Furthermore, CatC promoted the formation of TLSs in the brain, leading to persistent neuroinflammation and exacerbating the severity of EAE in the chronic phase. Conversely, treatment with AZD7986, a specific inhibitor of CatC, effectively attenuated the syndrome of EAE and its effects caused by CatC both in vivo and in vitro. These findings provide a novel insight into the critical role of CatC in innate and adaptive immunity in EAE, and specific inhibitor of CatC, AZD7986, may contribute to potential therapeutic strategies for MS.

CB11S3+: A Triangular Boron-Based Cluster with One Planar Tetracoordinate Carbon at Its Edge.

Boron-based clusters containing planar tetracoordinate carbon (ptC) are unique and scarce. Isoelectronic-replacing after proper vulcanization is an effective strategy to obtain the ptC based on the B12 cluster. Herein we report computational evidence for a ternary CB11S3+ (C2v, 1A1) cluster, which possesses a concentric double-triangle structure containing one ptC atom at the peripheral edge. The unbiased structural explorations of potential energy surfaces and high-level CCSD(T) calculations indicate that the ptC CB11S3+ cluster is a true global minimum. Born-Oppenheimer molecular dynamics (BOMD) simulations reveal that it is dynamically stable against isomerization and decomposition. Chemical bonding analysis reveals that three delocalized π bonds endow the π aromaticity to the CB11 unit of CB11S3+. In addition, the strong S → B π back-bonding is also conducive to the stability of CB11S3+. The current findings offer opportunities for further boron-based ptC clusters.

A genome-wide investigation of the mechanism underlying the effect of exogenous boron application on sugar content and overall quality of "Benihoppe" strawberries.

In recent years, the widespread application of growth regulators and nutrients to boost yield and quality of strawberry fruits has led to the rapid growth of strawberry industry globally. Although the effects of major nutrients on strawberry yield have been widely studied, investigations into the effect of trace elements such as boron remain limited. This study examined the effect of boron application on the yield and quality of "Benihoppe" strawberry fruits. Nutrient solutions with varying boron concentrations (0, 0.024, 0.048, 0.072, and 0.096 mM) were applied to the plants, and their effect on fruit quality was evaluated. The results indicated that boron application enhanced the yield per plant, nutrient composition (total amino acid and vitamin C content), antioxidant properties (total phenol) and volatile components (esters) in strawberry fruits. Specifically, treatment with 0.048 mM boron concentration significantly increased the accumulation of soluble sugars, such as sucrose, whose concentration was 154.29% higher than that of the control treated with 0 mM concentration. This enhancement is attributable to the regulated expression of sucrose phosphate synthase (maker-Fvb2-2-augustus-gene-229.38) and ß-fructofuranosidase-1/2/3 (augustus-masked-Fvb5-4-processed-gene-2.0, maker-Fvb5-3-augustus-gene-272.30, and maker-Fvb5-1-augustus-gene-0.37) genes, which play crucial roles in sugar metabolism and enzyme activity. Overall, boron application enhanced the quality of "Benihoppe" strawberries. The findings of this study offer substantial theoretical and practical guidance for using boron fertilizers in strawberry farming.

Target-specific affinity separation of the bioactive compounds from herbal extract using the spin column packed with the immobilized protein microspheres prior to LC-MS analysis.

Excellent pretreatments before instrumental analysis are critical for separation and determination of target compounds for discovery of new drugs from herb medicines. We developed a rapid and highly-selective method to separate the bioactive compounds from herbal extract using protein affinity-selection spin column, which was packed with the new sorbent materials from integrating the recombinant ß2-adrenoceptor (ß2-AR) directly out of cell lysates onto the surface of microspheres. Protein affinity-selection spin column was placed in a centrifugal tube, where after the non-specific binders were released to the filtrate under the operational centrifugation, the specific binders on the spin column were cleaned with a washing solvent for LC-MS analysis. The known agonists of ß2-AR were retained/released on protein affinity-selection spin column but not on control column, demonstrating the method with good recovery (79.4∼95.7 %) and high repeatability (RSD < 3.5 %). The adsorption features of three ligands on the spin column were described best by Prism saturation binding model, and the high-affinity binding and the large binding capacity of the spin column make it feasible to trap the trace analytes effectively. It was applied in separating bioactive compounds from Alstoniae Scholaris extract, two of which were identified as picrinine and oleanolic acid in combination with LC-MS and verified as the potential agonists towards ß2-AR though molecular docking and cell experiments. Our study demonstrated that, the spin column with the immobilized protein sorbents in the centrifugal filter device represents a promising tool, enabling rapid and target-specific affinity separation of the bioactive compounds from herbal extract.