Absence of PD-L1 signaling hinders macrophage defense against Mycobacterium tuberculosis via upregulating STAT3/IL-6 pathway.

The blockade of programmed death-ligand 1 (PD-L1) pathway has been clinically used in cancer immunotherapy, while its effects on infectious diseases remain elusive. Roles of PD-L1 signaling in the macrophage-mediated innate immune defense against M.tb is unclear. In this study, the outcomes of tuberculosis (TB) in wild-type (WT) mice treated with anti-PD-1/PD-L1 therapy and macrophage-specific Pdl1-knockout (Pdl1ΔΜΦ) mice were compared. Treatment with anti-PD-L1 or anti-PD-1 benefited protection against M.tb infection in WT mice, while Pdl1ΔΜΦ mice exhibited the increased susceptibility to M.tb infection. Mechanistically, the absence of PD-L1 signaling impaired M.tb killing by macrophages. Furthermore, elevated STAT3 activation was found in PD-L1-deficient macrophages, leading to increased interleukin (IL)-6 production and reduced inducible nitric oxide synthase (iNOS) expression. Inhibiting STAT3 phosphorylation partially impeded the increase in IL-6 production and restored iNOS expression in these PD-L1-deficient cells. These findings provide valuable insights into the complexity and mechanisms underlying anti-PD-L1 therapy in the context of tuberculosis.

[Clinical observation of sinus tarsi syndrome after lateral ankle sprain].

OBJECTIVE: To study the incidence rate of sinus tarsi syndrome after lateral ankle sprain and observe the clinical efficacy of sinus tarsal corticosteroid injections. METHODS: From January 2021 to Janury 2022, 391 patients with lateral ankle sprain and 88 patients with sinus tarsi syndrome using corticosteroid injections (compound betamethasone 1 ml+ lidocaine hydrochloride 4 ml) were retrospectively analyzed. There were 22 males and 66 females, aged from 29 to 60 years old with an average of (41.00±7.52) years old, duration of the disease from 1 to 12 months with an average of (5.6±4.2) months. The visual analogue scale(VAS) and American Orthopedic Foot and Ankle Society(AOFAS) scores were collected before, 1 month, 3 months, 6 months, and 12 months after treatment. RESULTS: All 88 patients completed a 12-month follow-up. The incidence rate of sinus tarsi syndrome after lateral ankle sprain was 22.5%. One month after treatment, VAS was 1.20±0.89, AOFAS score was 88.70±7.04. Three months after treatment, VAS was 1.60±1.35, AOFAS score was 85.20±10.95. Six months after treatment, VAS 2.35±1.39, AOFAS 80.30±9.75. Twelve months after treatment, VAS was 2.80±1.51, AOFAS score was 79.1±9.94. Significant differences were found before and after treatment at all four time points of follow-up(P<0.05). CONCLUSION: The results of this study showed that the incidence rate of sinus tarsi syndrome after lateral ankle sprain was 22.5%. Corticosteroid injections were effective in the short term with a 65% recurrence rate of symptoms within 1 year. For patients with no significant long-term effect of conservative treatment, clinicians may explore alternative approaches, including options like ankle arthroscopy.

Sandwiched film of graphene/silver nanowire conductive layer reinforced by hydroxyethyl cellulose bond layer.

Multilayer nanocomposite film made of different materials has multifunctional properties and is applied in the field of flexible electronic devices. Herein, hydroxyethyl cellulose (HEC) and boron nitride nanosheets (BNNS) were used as the matrix and thermal conductivity material of the HEC/BNNS (HB) insulation layer and were combined with conductive blade structure graphene/silver nanowires (GA) film to prepare a three-layer HB/GA20/HB film. Using the high mechanical properties of the HEC based film, the tensile strength of the three-layer film is increased to 22.0 MPa, 633 % higher than that of the pure conductive film. The sensor prepared by multilayer film has good bending sensing performance (1500 cycles) and electromagnetic shielding performance (29.3 dB). The heating temperature of HB/GA20/HB film heater is up to 107.9 °C at 20 V. In the HB/GA20/HB film, the external HB layer provides insulation, thermal conductivity and physical support, and the internal GA layer with good conductive and sensing properties is combined to build a multi-functional sensor, which can be applied as a mobile sensor, heater and electromagnetic shielding material in the flexible wearable field.

Efficient mercury(II) removal by corn bract/dopamine@ZnS composites.

In this study, we have utilized corn bract, a green agricultural by-product, as a carrier. It is subsequently modified with zinc sulfide to synthesize an efficient composite material termed as corn bract/polydopamine@zinc sulfide (CB/PDA@ZnS). This novel composite demonstrates significant potential for biomass removal of mercury ions (Hg(II)). The composition, structure, and morphology of CB/PDA@ZnS composites are characterized by Fourier transform infrared (FT-IR) spectrum, thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), and scanning electron microscope (SEM). The effect of pH value, adsorbent dosage, initial Hg(II) concentration, adsorption time and temperature, and coexistence ions on the adsorption behavior is investigated. The results show that CB/PDA@ZnS can efficiently remove Hg(II) from water with uptake capacities of 333.03 mg/g and removal efficiency of 99.91% under an optimal conditions (pH of 3, the adsorbent dosage of 0.015 g, contact time of 90 min, and initial concentration of 100 mg/L) at room temperature. The fitting analysis of the experimental data reveals that the adsorption process of Hg(II) follows the quasi-secondary adsorption kinetic model as well as the Langmuir isothermal adsorption model, which is a spontaneous heat absorption process. In addition, the composite adsorbent obtained exhibit excellent selectivity for Hg(II) ions and anti-coexisting ion interference performance. After five cycles of adsorption-desorption experiments, the corresponding adsorption capacity is 331.11 mg/g, accounting for 93.33% of the first adsorption capacity, indicating that the adsorbent has excellent regeneration performance. The stability of the adsorbent and the adsorption mechanism of Hg(II) ion are systematically discussed using FT-IR, XRD, and X-ray photoelectron spectroscopy (XPS). Finally, this adsorbent is tested for the removal of industrial wastewater containing Hg(II), and the adsorption and removal efficiency are 331.67 mg/g and 99.50%, respectively. This study provides a very valuable information for future Hg(II) removal from aqueous solutions.

HDAC2 Inhibits Hippocampal Neurogenesis and Impairs the Cognitive Function in Prenatally Stressed Adult Offspring / HDAC2 Inhibe la Neurogénesis del Hipocampo y Afecta la Función Cognitiva en la Descendencia Adulta Estresada Prenatalmente

SUMMARY: The objective of this study was to investigate the mechanism of prenatal stress on the cognitive function of offspring, and clarify the change of histone deacetylase 2 (HDAC2) expression in hippocampal neurons of offspring. 16 pregnant SD rats were randomly divided into control group and stress group, with eight rats in each group. The stress group received restrained stress from 15 to 21 days of pregnancy, while the control group did not receive any treatment. Anxiety-like behavior and spatial memory, learning and memory ability were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. Nissl staining was used to detect the function of hippocampal neurons. Western blot was used to detect the expression of HDAC2 protein in hippocampal neurons of adult offspring. Immunofluorescence staining was used to detect the expression of HDAC2 protein and hippocampal neurogenesis. The learning and memory ability of adult offspring was decreased. The prenatal stress damaged the function of hippocampal neurons , the expression of HDAC2 was down-regulated, and the number of neurons was reduced. Maternal prenatal stress can down- regulate the expression of HDAC2 in the hippocampus of offspring, inhibits hippocampal neurogenesis and impairs the cognitive function.

El objetivo de este estudio fue investigar el mecanismo del estrés prenatal en la función cognitiva de la descendencia y aclarar el cambio de la expresión de la histona desacetilasa 2 (HDAC2) en las neuronas del hipocampo de la descendencia. 16 ratas SD preñadas se dividieron aleatoriamente en un grupo de control y un grupo de estrés, con ocho ratas en cada grupo. El grupo de estrés recibió estrés durante 15 a 21 días de pre, preñez, mientras que el grupo de control no recibió ningún tratamiento. El comportamiento similar a la ansiedad y la memoria espacial, el aprendizaje y la capacidad de memoria se detectaron en campo abierto, laberinto en cruz elevado, prueba de reconocimiento de objetos novedosos y laberinto de Barnes. La tinción de Nissl se utilizó para detectar la función de las neuronas del hipocampo. Se utilizó Western blot para detectar la expresión de la proteína HDAC2 en las neuronas del hipocampo de la descendencia adulta. La tinción de inmunofluorescencia se utilizó para detectar la expresión de la proteína HDAC2 y la neurogénesis del hipocampo. La capacidad de aprendizaje y memoria de la descendencia adulta se redujo. El estrés prenatal dañó la función de las neuronas del hipocampo, se reguló negativamente la expresión de HDAC2 y se redujo el número de neuronas. El estrés prenatal materno puede regular a la baja la expresión de HDAC2 en el hipocampo de la descendencia, inhibe la neurogénesis del hipocampo y deteriora la función cognitiva.

Bacillus Calmette-Guérin-induced interleukin-10 inhibits S100A8/A9 production and hinders development of T helper type 1 memory in mice.

Tuberculosis caused by Mycobacterium tuberculosis (M.tb) is one of the main causes of human death in the world. Bacillus Calmette-Guérin (BCG) provides limited protection in adolescents and adults. To explore the factors reducing efficacy of BCG vaccine, we assess the impacts of interleukin (IL)-10 and alarmins S100A8/A9 on T-cell memory. We found that BCG-induced IL-10 inhibited production of S100A8/A9 in human peripheral blood mononuclear cells (PBMCs) and murine splenocytes. S100A9 deficiency inhibited IFN-γ production by CD4+ T cells in the early phase of BCG immunization and hindered the development of effector memory T helper type 1 (Th1) cells, while IL-10 deficiency promoted Th1 memory and blocking IL-10 signaling enhanced Th1 protective recall response against M.tb. IL-10 inhibited the binding of transcription factor CCAAT enhancer binding protein beta to S100a8/a9 promoter leading to S100A8/A9 reduction. S100A8/A9 heterodimer enhanced the IFN-γ production via receptor for advanced glycation end products signaling in CD4+ T cells. Our results demonstrate a hurdle to development of Th1 memory after BCG immunization and clarify the mechanism of the regulation of Th1 memory by IL-10 and S100A8/A9.

Highly effective removal of Hg(ii) solution using corn bract@MoS2 as a new biomass adsorbent.

As known, mercury contamination is one of the current environmental issues due to the high toxicity of mercury. Corn bract (CB) is an agricultural by-product, and its final treatment is generally incineration that causes air pollution. In this study, a new type of high-efficiency biomass adsorbent (CB@MoS2) for adsorption of Hg(ii) was obtained, and its morphology and structure were characterized with FT-IR, XRD, SEM and TEM. The results showed that when the pH value, Hg(ii) ion concentration and adsorption time were 4, 100 mg L-1 and 120 min, the adsorption capacity and removal rate could reach 332.50 mg g-1 and 99.75%. In addition, CB@MoS2 had a good selectivity for Hg(ii) ions. The adsorption behavior followed pseudo-second-order kinetics, indicating that the adsorption of Hg(ii) ions by CB@MoS2 was a chemical adsorption. After five adsorption-desorption experiments, it still possessed good adsorption performance and effective regeneration. In short, CB@MoS2 has high efficiency and good reusability, and will become a candidate material for the treatment of mercury-containing industrial wastewater.

Effect of bone-shaped nanotube-hydrogel drug delivery system for enhanced osseointegration.

Anodic titanium dioxide nanotubes (TNT) have a range of beneficial theranostic properties. However, a lack of effective osseointegration is a problem frequently associated with the titanium dental implant surface. Here, we investigated whether bone-shaped nanotube titanium implants could enhance osseointegration via promoting initial release of vascular endothelial growth factor 165 (VEGF165) and dual release of recombinant human bone morphogenetic protein-2 (rhBMP-2). Thus, we generated cylindrical-shaped nanotubes (TNT1) and bone-shaped nanotubes (TNT2) through voltage-varying and time-varying electrochemical anodization methods, respectively. Additionally, we prepared rhBMP-2-loaded cylindrical-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F1) and rhBMP-2-loaded bone-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F2) drug delivery systems. We evaluated the characteristics and release kinetics of the drug delivery systems, and then analyzed the cytocompatibility and osteogenic differentiation of these specimens with mesenchymal stem cells (MSCs) in vitro. Finally, we utilized a rat femur defect model to test the bone formation capacity of nanotube-hydrogel drug delivery system in vivo. Among these different nanotubes structures, the bone-shaped one was the optimum structure for growth factor release.

Multi-omics molecular biomarkers and database of osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis in the adult population and is a leading cause of disability. OA-related genetic loci may play an important role in clinical diagnosis and disease progression. With the rapid development of diverse technologies and omics methods, many OA-related public data sets have been accumulated. Here, we retrieved a diverse set of omics experimental results from 159 publications, including genome-wide association study, differentially expressed genes and differential methylation regions, and 2405 classified OA-related gene markers. Meanwhile, based on recent single-cell RNA-seq data from different joints, 5459 cell-type gene markers of joints were collected. The information has been integrated into an online database named OAomics and molecular biomarkers (OAOB). The database (http://ibi.zju.edu.cn/oaobdb/) provides a web server for OA marker genes, omics features and so on. To our knowledge, this is the first database of molecular biomarkers for OA.

PlantcircBase 7.0: Full-length transcripts and conservation of plant circRNAs.

Circular RNA (circRNA) is a special type of non-coding RNA that participates in diverse biological processes in both animals and plants. Five years ago, we developed a comprehensive plant circRNA database (PlantcircBase), which has attracted much attention from the plant circRNA community. Here, we report an updated PlantcircBase (v.7.0), which contains 171,118 circRNAs from 21 plant species. Over 31,000 of the circRNAs have full-length sequences constructed based on analysis of 749 bulk RNA sequencing (RNA-seq) datasets downloaded from the public domain and Nanopore long-read sequencing results of rice RNAs newly generated in this study. A plant multiple conservation score (PMCS), based on the conservation of both sequence and expression profiles, was calculated for each circRNA to quantify and compare the conservation of all circRNAs. A new parameter, plant circRNA confidence level (PCCL), is introduced to measure the identity reliability of each circRNA based on experimental validation results and the number of references that support the circRNA. All this information and other details of circRNAs can be browsed, searched, and downloaded from PlantcircBase 7.0, which also provides online bioinformatics tools for visualization and sequence alignment. PlantcircBase 7.0 is publicly and freely accessible at http://ibi.zju.edu.cn/plantcircbase/.

In Situ Loading of Polypyrrole onto Aramid Nanofiber and Carbon Nanotube Aerogel Fibers as Physiology and Motion Sensors.

Nanocomposite conductive fiber has been newly developed as a lightweight material with high flexibility and strong weavability, which can meet the requirements of flexible wearable devices. Herein, lightweight porous aramid nanofibers (ANF) and carbon nanotube (CNT) aerogel fibers coated with polypyrrole (PPy) layers are prepared by a wet spinning method for motion detection and information transmission. The ANF/CNT/PPy aerogel fiber with low density (56.3 mg/cm3), conductivity (6.43 S/m), and tensile strength (2.88 MPa) were used as motion sensors with high sensitivity (0.12) and long life (1000 cycles). At the same time, the differential conductivity of aerogel fibers is utilized to reduce the information transmission time (up to 46%). High- and low-temperature-resistant (-196 to 100 °C) aerogel fibers are also available as a quick heater and ionic solution detector. In summary, the prepared ANF/CNT/PPy aerogel fiber can be used as a multifunctional sensor for human-health detection and motion monitoring.

Recent origination of circular RNAs in plants.

Circular RNA (circRNA) is a kind of new regulatory RNA with diverse biological functions. Numerous circRNAs have been identified in many plant species; however, evolution of plant circRNAs remains largely unknown. In this study, we assembled full-length sequences of 6519 rice (Oryza sativa) circRNAs and analyzed their conservation in another 46 plant species based on comparison of sequences and expression patterns. We found that, at the genomic level, 8.7% of the 6519 circRNAs were conserved in dicotyledonous plants and 49.1% in Oryza genus. Meanwhile, 57.8% of parental protein-coding genes of the rice circRNAs originated recently after divergence of monocotyledonous plants, implying recent origin of the majority of rice circRNAs, a conclusion further supported by the results based on analysis of 4663 full-length circRNAs in Arabidopsis thaliana. Accordingly, we proposed three models to address the origination of different types of circRNAs. Taken together, the results obtained in this study provide new insights for the evolutionary dynamics of plant circRNAs and candidate circRNAs for further functional exploration.

Biocompatible Nanotube-Strontium/polydopamine-arginine-glycine-aspartic acid coating on Ti6Al4V enhances osteogenic properties for biomedical applications.

Titanium (Ti) alloys, particularly Ti6 Al4 V, are the most commonly used biomedical implant material. Ti alloys are biologically inert, so there have been continuous efforts to improve their osteogenic properties and clinical performance. Since TiO2 nanotubes (NT) appear to be excellent drug platforms, and strontium reportedly enhances osteogenesis, we constructed a TiO2 nanotube coating on the surface of Ti6 Al4 V and immersed it in Sr (OH)2 solution in order to incorporate Sr into TiO2 nanotubes (NT-Sr). The results of field emission scanning electron microscope and X-ray diffraction analysis verified the fabrication of NT-Sr. We next added polydopamine (PDA) and cyclo- (arginine-glycine-aspartic acid-phenylalanine-cysteine) [c(RGDfC)] peptides to further promote biocompatibility of the implant. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the existence of PDA and c(RGDfC). Mesenchymal stem cells (MSCs) were planted on Ti, NT, NT-Sr, NT-Sr/PDA, and NT-Sr/PDA-RGD surfaces. The adhesion and differentiation of MSCs on different surfaces were evaluated. The mRNA expression of alkaline phosphatase, runt-related transcription factor 2 (Runx2) and type I collagen (Col I) of different groups were also tested. Finally, we observed that the NT-Sr/PDA-RGD group showed significantly better performance than other groups in terms of the differentiation and osteogenesis-related gene expression of MSCs. Thus, the NT-Sr/PDA-RGD complex may be an important modification strategy for Ti, as it shows excellent osteogenic potential.

Preparation of new diatomite-chitosan composite materials and their adsorption properties and mechanism of Hg(II).

A new composite absorbent with multifunctional and environmental-friendly structures was prepared using chitosan, diatomite and polyvinyl alcohol as the raw materials, and glutaraldehyde as a cross-linking agent. The structure and morphology of the composite absorbent, and its adsorption properties of Hg(II) in water were characterized with Fourier transform infrared (FT-IR) spectra, scanning electron microscope (SEM), X-ray diffraction (XRD), Brunauer Emmett Teller (BET) measurements and ultraviolet-visible (UV-Vis) spectra. The effect of the pH value and contact time on the removal rate and absorbance of Hg(II) was discussed. The adsorption kinetic model and static adsorption isotherm and regeneration of the obtained composite absorbent were investigated. The results indicated that the removal of Hg(II) on the composite absorbent followed a rapid adsorption for 50 min, and was close to the adsorption saturation after 1 h, which is in accord with the Langmuir adsorption isotherm model and the pseudo-second-order kinetic model. When the pH value, contact time and the mass of the composite absorbent was 3, 1 h and 100 mg, respectively, the removal rate of Hg(II) on the composite absorbent reached 77%, and the maximum adsorption capacity of Hg(II) reached 195.7 mg g-1.