Chiral Stacking Identification of Two-Dimensional Triclinic Crystals Enabled by Machine Learning.

Chiral materials possess broken inversion and mirror symmetry and show great potential in the application of next-generation optic, electronic, and spintronic devices. Two-dimensional (2D) chiral crystals have planar chirality, which is nonsuperimposable on their 2D enantiomers by any rotation about the axis perpendicular to the substrate. The degree of freedom to construct vertical stacking of 2D monolayer enantiomers offers the possibility of chiral manipulation for designed properties by creating multilayers with either a racemic or enantiomerically pure stacking order. However, the rapid recognition of the relative proportion of two enantiomers becomes demanding due to the complexity of stacking orders of 2D chiral crystals. Here, we report the unambiguous identification of racemic and enantiomerically pure stackings for layered ReSe2 and ReS2 using circular polarized Raman spectroscopy. The chiral Raman response is successfully manipulated by the enantiomer proportion, and the stacking orders of multilayer ReSe2 and ReS2 can be completely clarified with the help of second harmonic generation and scanning transmission electron microscopy measurements. Finally, we trained an artificial intelligent Spectra Classification Assistant to predict the chirality and the complete crystallographic structures of multilayer ReSe2 from a single circular polarized Raman spectrum with the accuracy reaching 0.9417 ± 0.0059.

Fabricating Ultrastrong Carbon Nanotube Fibers via a Microwave Welding Interface.

Liquid crystal wet-spun carbon nanotube fibers (CNTFs) offer notable advantages, such as precise alignment and scalability. However, these CNTFs usually suffer premature failure through intertube slippage due to the weak interfacial interactions between adjacent shells and bundles. Herein, we present a microwave (MW) welding strategy to enhance intertube interactions by partially carbonizing interstitial heterocyclic aramid polymers. The resulting CNTFs exhibit ultrahigh static tensile strength (6.74 ± 0.34 GPa) and dynamic tensile strength (9.52 ± 1.31 GPa), outperforming other traditional high-performance fibers. This work provides a straightforward yet effective approach to strengthening CNTFs for advanced engineering applications.

Paraffin-Enabled Superlattice Customization for a Photostimulated Gradient-Responsive Artificial Reflex Arc.

The development of photostimulated-motion artificial reflex arcs - a neural circuit inspired by light-driven motion reflexes - holds significant promises for advancements in robotic perception, navigation, and motion control. However, the fabrication of such systems, especially those that accommodate multiple actions and exhibit gradient responses, remains challenging. Here, a gradient-responsive photostimulated-motion artificial reflex arc is developed by integrating a programmable and tunable photoreceptor based on folded MoS2 at different twist angles. The twisted folded bilayer MoS2 used as photoreceptors can be customized via the transfer technique using patternable paraffin, where the twist angle and fold-line could be controlled. The photoluminescence (PL) intensity is 3.7 times higher at a twist angle of 29° compared to that at 0°, showing a monotonically decreasing indirect bandgap. Through tunable interlayer carrier transport, photoreceptors fabricated using folded bilayer MoS2 at different twist angles demonstrate gradient response time, enabling the photostimulated-motion artificial reflex arc for multiaction responses. They are transformed to digital command flow and studied via machine learning to control the gestures of a robotic hand, showing a prototype of photostimulated gradient-responsive artificial reflex arcs for the first time. This work provides a unique idea for developing intelligent soft robots and next-generation human-computer interfaces.

Serum thyroid function, hs-CRP expression, and coagulation function in syphilis patients / 公共卫生与预防医学

Objective To investigate the serum levels of thyroid function and hs-CRP expression in patients with syphilis and their relationship with coagulation function. Methods A total of 80 syphilis patients admitted to Bazhong Central Hospital from January 2020 to January 2022 were selected as the study subjects and set as the observation group. In addition, 80 healthy individuals were selected as the control group, and 80 psoriasis patients were selected as the disease control group. Thyroid function, hs-CRP and coagulation function among different groups were compared. The correlation between thyroid function, hs-CRP, and coagulation function in patients with syphilis was analyzed, and the effectiveness of these parameters in predicting syphilis was analyzed. Results The values of FT3, FT4, TSH and hs-CRP in the observation group were higher than those in the control group and the disease control group (P<0.05). The abnormal rates of thyroid function and hs-CRP level in the observation group were higher than those in the control group and the disease control group (P<0.05). PT, APTT, and TT of the observation group were higher than those of the control group and the disease control group (P<0.05). The abnormal rate of coagulation function in the observation group was higher than that in the control group and the disease control group (P<0.05). The levels of FT3, FT4, TSH, hs-CRP, PT, APTT, and TT in the first stage were lower than those in the second and third stages, while these parameters in the secondary stage were lower than those in the third stage (P<0.05). The severity of syphilis was positively correlated with FT3, FT4, hs-CRP, APTT, and TT (P<0.05). Among these indicators, TT was more effective in the diagnosis of syphilis. Conclusion Syphilis patients have hyperthyroidism, accompanied by coagulation dysfunction and abnormal increase in hs-CRP, which are all related to the condition of syphilis patients. The combined prediction of syphilis patients has high effectiveness.

Esophageal cancer cell-derived small extracellular vesicles decrease circulating Tfh/Tfr via sEV-PDL1 to promote immunosuppression.

Esophageal cancer (EC) is a deadly malignancy. Small extracellular vesicles (sEVs) with programmed death ligand 1 (sEV-PDL1) induce immune escape to promote tumor progression. Furthermore, the imbalance between circulating follicular helper T (Tfh) and circulating follicular regulatory T (Tfr) cells is related to the progression of many malignant tumors. However, the role of the EC-derived sEV-PDL1 in circulating Tfh/Tfr is unknown. Circulating Tfh and Tfr cells were detected by flow cytometry. sEVs were isolated through differential centrifugation and cultured for cell expansion assays. Naïve CD4+ T cells were isolated, stimulated, and cultured with sEVs to evaluate the frequencies, phenotypes, and functions of Tfh and Tfr cells. The proportion of circulating Tfh in patients with EC was lower than that in healthy donors (HDs), whereas that of circulating Tfr was higher. The EC group showed significantly lower circulating Tfh/Tfr and a higher level of sEV-PDL1 than HDs. Notably, sEV-PDL1 was negatively correlated with circulating Tfh/Tfr in the EC group. In vitro assays, sEV-PDL1 inhibited Tfh expansion, enhanced the cytotoxic T lymphocyte-associated antigen 4+ (CTLA4+) Tfh cell percentage, decreased the levels of interleukin (IL)-21 and interferon-γ, and increased IL-10. sEV-PDL1 promoted the expansion and immunosuppressive functions of circulating Tfr; the increased percentages of CTLA4+ Tfr and inducible T cell co-stimulator+ Tfr were accompanied with high IL-10. However, applying an anti-PDL1 antibody significantly reversed this. Our results suggest a novel mechanism of sEV-PDL1-mediated immunosuppression in EC. Inhibiting sEV-PDL1 to restore circulating Tfh/Tfr balance provides a novel therapeutic approach for EC.

Enhanced Layer-Breathing Modes in van der Waals Heterostructures Based on Twisted Bilayer Graphene.

The characterization of interlayer coupling in two-dimensional van der Waals heterostructures (vdWHs) is essential to understand their quantum behaviors and structural functionalities. Interlayer shear and layer-breathing (LB) phonons carry rich information on interlayer interaction, but they are usually too weak to be detected via standard Raman spectroscopy due to the weak electron-phonon coupling (EPC). Here, we report a universal strategy to enhance LB modes of vdWHs based on twisted bilayer graphene (tBLG). In both tBLG/hBN and tBLG/MoS2 vdWHs, the resonantly excited electrons in tBLG can strongly couple to LB phonons extended over the entire layers in the vdWHs, whose resonance condition is tunable by the twist angle of tBLG. In vdWHs containing twisted graphene layers with multiple twisted interfaces, the EPC of LB phonons coming from the collective LB vibrations of entire heterostructure layers can be tuned by resonant excitation of programmable van Hove singularities according to each twisted interface. The universality and tunability of enhanced LB phonons by tBLG make it a promising method to investigate EPC and interlayer interaction in related vdWHs.

TGF-ß3 in differentiation and function of Tph-like cells and its relevance to disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: T peripheral helper (Tph) cells have major roles in pathological processes in SLE. We sought to clarify the mechanisms of Tph cell differentiation and their relevance to clinical features in patients with SLE. METHOD: Phenotypes and functions of Tph cell-related markers in human CD4+ T cells purified from volunteers or patients were analysed using flow cytometry and quantitative PCR. Renal biopsy specimens from patients with LN were probed by multicolour immunofluorescence staining. RESULTS: Among multiple cytokines, transforming growth factor (TGF)-ß3 characteristically induced programmed cell death protein 1 (PD-1)hi musculoaponeurotic fibrosarcoma (MAF)+, IL-21+IL-10+ Tph-like cells with a marked upregulation of related genes including PDCD-1, MAF, SOX4 and CXCL13. The induction of Tph-like cells by TGF-ß3 was suppressed by the neutralization of TGF-ß type II receptor (TGF-ßR2). TGF-ß3-induced Tph-like cells efficiently promoted the differentiation of class-switch memory B cells into plasmocytes, resulting in enhanced antibody production. The proportion of Tph cells in the peripheral blood was significantly increased in patients with SLE than in healthy volunteers in concordance with disease activity and severity of organ manifestations such as LN. TGF-ß3 was strongly expressed on macrophages, which was associated with the accumulation of CD4+ C-X-C chemokine receptor (CXCR5)-PD-1+ Tph cells, in the renal tissue of patients with active LN. CONCLUSION: The induction of Tph-like cells by TGF-ß3 mainly produced from tissue macrophages plays a pivotal role in the pathological processes of active LN by enhancing B-cell differentiation in patients with SLE.

The association between rotavirus diarrhea in children and atmospheric pressure in Guangzhou City from 2012 to 2020 / 中国学校卫生

Objective@#To explore the relative risks of rotavirus diarrhea after exposure to different levels of atmospheric pressure in children in Guangzhou City, so as to provide reference for improving public awareness of high atmospheric pressure exposure.@*Methods@#The study used the China Notifiable Communicable Diseases Network System and China Meteorological Science Data Sharing Service Network to collect meteorological data and data relating to daily cases of rotavirus diarrhea in children at Guangzhou Women and Children s Medical Center from 2012 to 2020. The association between rotavirus diarrhea and atmospheric pressure was analyzed using distributed lag non linear models (DLNM). The relative risks of different sex and age sub groups exposed to different atmospheric pressures were also evaluated.@*Results@#A total of 18 587 cases of rotavirus diarrhea were reported from 2012 to 2020, among which 11 662 cases (62.7%) were boys, and 12 582 cases (67.7%) were children aged 6 to 24 months old, which represented the highest proportion. The results of the DLNM showed that the relative risk of rotavirus diarrhea was the highest on the day of exposure to extreme high atmospheric pressure ( RR =1.50, 95% CI =1.24-1.82, P <0.05) and the effect could last for 28 days. Risk of rotavirus diarrhea was low for exposure to low pressure within 2 weeks ( P <0.05). During extremely high atmospheric pressure weather, RR was higher in girls ( RR =3.31, 95% CI =1.46-7.49， P <0.05) than that in boys ( RR =1.98, 95% CI =0.96-4.07， P >0.05). Among different age sub groups, RR was the highest in children aged 24 to 60 months after exposure to the highest level of atmospheric pressure exposure ( RR =3.36, 95% CI =1.27-8.89, P <0.05).@*Conclusion@#In Guangzhou, exposure to high pressure increases the risk of rotavirus diarrhea in children. In the future, public awareness should be raised regarding the risk after exposure to high atmospheric pressure.

Epstein-Barr virus-induced gene 3 commits human mesenchymal stem cells to differentiate into chondrocytes via endoplasmic reticulum stress sensor.

Mesenchymal stem cells (MSC) can differentiate into chondrocytes. Epstein-Barr virus-induced gene 3 (EBI3) is differentially expressed during chondrogenic differentiation and can be produced by MSC. EBI3 is also a subunit of interleukin (IL)-27 and IL-35, and it accumulates in the endoplasmic reticulum (ER) when its partners, such as IL-27 p28 and IL-35 p35, are insufficient. ER stress induced by protein accumulation is responsible for chondrogenic differentiation. However, the role of EBI3 and its relevance to the ER stress in chondrogenic differentiation of MSC have never been addressed. Here, we demonstrate that EBI3 protein is expressed in the early stage of chondrogenic differentiation of MSC. Additionally, knockdown, overexpression, or induction of EBI3 through IL-1ß inhibits chondrogenesis. We show that EBI3 localizes and accumulates in the ER of MSC after overexpression or induction by IL-1ß and TNF-α, whereas ER stress inhibitor 4-phenylbutyric acid decreases its accumulation in MSC. Moreover, EBI3 modulates ER stress sensor inositol-requiring enzyme 1 α (IRE1α) after induced by IL-1ß, and MSC-like cells coexpress EBI3 and IRE1α in rheumatoid arthritis (RA) synovial tissue. Altogether, these data demonstrate that intracellular EBI3 commits to chondrogenic differentiation by regulating ER stress sensor IRE1α.

Analysis of Ecological Environment Problems and Countermeasures in Ideological and Political Education in Colleges and Universities.

At present, there are many problems in the mode and method of ideological and emotional education of college students. The state attaches great importance to this aspect and continues to increase investment, but the effect is not satisfactory. As an important field for cultivating high-level socialist talents, colleges and universities have played a huge role in promoting the ideological development and emotional education of college students. The emergence of this contradiction shows that traditional educational methods have their own shortcomings and need to expand their thinking and explore new research areas. Since the new era, the ideological education venues and teaching activities of colleges and universities have been greatly improved, but they are also facing many problems and challenges, which seriously affect the moral quality of college students and destroy the ideological education ecosystem of colleges and universities. From the perspective of the ecological crisis of education, this paper awakens and pays attention to the ecological problems of education, making it an inevitable trend of current education development and paving the way for future research. On this basis, the current situation of the ecology of political education of college students is analyzed, and the necessity of research is proposed. Analyzing the ideological and emotional education of college students from the perspective of ecology is essentially to regard the ideological education of college students as an ecosystem and deeply analyze the distribution of various components and elements of college students' ideological and political education. The ecology of college students' ideological education is the process, law, and overall ecological balance of various factors in the ideological education system of college students, as well as the methodological thinking and value orientation of the interaction between various factors and the environment. The changes of the ecological environment have a significant impact on people's state of mind. As college students growing up in the new environment, their thoughts, emotions, and values are all affected by the development of the ecological environment. Therefore, changes in the ecological environment, air quality, and water environment have increasingly obvious impacts on the living environment.

mTOR activation in CD8+ cells contributes to disease activity of rheumatoid arthritis and increases therapeutic response to TNF inhibitors.

OBJECTIVE: This study aimed to understand the role of mammalian target of rapamycin (mTOR) in CD8+ cells in the pathogenicity of RA and the changes after treatment with biologic drugs. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 17 healthy controls and 86 patients with RA. Phosphorylation of mTOR (p-mTOR) and its clinical relevance were evaluated. The role of mTOR in CD8+ cells was also examined in vitro. RESULTS: Patients with RA who had a moderate or high disease activity, were biologic-naïve, and were refractory to MTX were enrolled in this study. The p-mTOR levels in CD8+ cells were higher in patients with RA than in healthy controls, and they positively correlated with the disease activity in such patients. However, after one year of treatment with TNF inhibitors, the p-mTOR levels in CD8+ cells were suppressed and showed a positive correlation with the treatment response, which was not observed in the abatacept-treatment group. In vitro stimulation of CD8+ cells with anti-CD3 and anti-CD28 antibodies induced mTOR phosphorylation and increased the production of granzyme B, granulysin, TNF-α and IFN-γ but decreased the production of granzyme K. However, on treatment with TNF inhibitors, p-mTOR levels in CD8+ cells and granzyme B production decreased, while granzyme K production increased. The production of granulysin and IFN-γ was not affected by the TNF inhibitors. CONCLUSION: These results suggested that mTOR activation in CD8+ cells may be a novel evaluation marker for RA disease activity and a predictive marker of therapeutic response to TNF inhibitors.

Microencapsulated phage composites with increased gastrointestinal stability for the oral treatment of Salmonella colonization in chicken.

Salmonella infection, one of the common epidemics in the livestock and poultry breeding industry, causes great economic losses worldwide. At present, antibiotics are the most commonly used treatment for Salmonella infection, but the widespread use of antibiotics has increased drug resistance to Salmonella. Phage therapy has gradually become an alternative method to control Salmonella infection. However, phage, a specific virus that can infect bacteria, has poor stability and is prone to inactivation during treatment. Microencapsulated phage microspheres can effectively solve this problem. Accordingly, in this study, Salmonella phages were microencapsulated, using the xanthan gum/sodium alginate/CaCl2/chitooligosaccharides method, to improve their gastrointestinal stability. Furthermore, microencapsulated phages were evaluated for in vitro temperature and storage stability and in vivo therapeutic effect. Phage microspheres prepared with 1 g/100 mL xanthan gum, 2 g/100 mL sodium alginate, 2 g/100 mL CaCl2, and 0.6 g/100 mL chitooligosaccharides were regular in shape and stable in the temperature range of 10-30°C. Also, microencapsulated phages showed significantly improved stability in the simulated gastric juice environment than the free phages (p < 0.05). In the simulated intestinal fluid, microencapsulated phages were completely released after 4 h. Moreover, microencapsulated phages showed good storage stability at 4°C. In the in vivo experiments detecting Salmonella colonization in the intestinal tract of chicks, microencapsulated phages showed a better therapeutic effect than the free phages. In conclusion, microencapsulated phages exhibited significantly improved stability, gastric acid resistance, and thereby efficacy than the free phages. Microencapsulated phages can be potentially used as biological control agents against bacterial infections.

Epidemiological characteristics of local COVID-19 epidemics and control experience in routine prevention and control phase in China / 中华流行病学杂志

The COVID-19 pandemic is still ongoing in the world, the risk of COVID-19 spread from other countries or in the country will exist for a long term in China. In the routine prevention and control phase, a number of local COVID-19 epidemics have occurred in China, most COVID-19 cases were sporadic ones, but a few case clusters or outbreaks were reported. Winter and spring were the seasons with high incidences of the epidemics; border and port cities had higher risk for outbreaks. Active surveillance in key populations was an effective way for the early detection of the epidemics. Through a series of comprehensive prevention and control measures, including mass nucleic acid screening, close contact tracing and isolation, classified management of areas and groups at risk, wider social distancing and strict travel management, the local COVID-19 epidemics have been quickly and effectively controlled. The experiences obtained in the control of the local epidemics would benefit the routine prevention and control of COVID-19 in China. The occurrence of a series of COVID-19 case clusters or outbreaks has revealed the weakness or deficiencies in the COVID-19 prevention and control in China, so this paper suggests some measures for the improvement of the future prevention and control of COVID-19.

Clinical Effect of Xijiao Dihuangtang Combined with Acupuncture on Treatment of Systemic Lupus Erythematosus with Syndrome of Intense Heat Toxin / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Xijiao Dihuangtang combined with acupuncture on the treatment of systemic lupus erythematosus （SLE） with syndrome of intense heat toxin. MethodA total of 102 cases of SLE with syndrome of intense heat toxin （admitted from January 2020 to December 2021） were divided into a control group and an observation group by random number table method， with 51 cases in each group. Patients in the control group received conventional western medicine treatment （hydroxychloroquine sulfate + poonisone acetate tablets）. Patients in the observation group were given Xijiao Dihuangtang combined with acupuncture based on the treatment of the control group. Clinical efficacy， onset time， symptom improvement time， skin lesion regression time， and hospital stays were recorded. Blood routine index change， 24 h urine protein levels， double-stranded DNA （ds-DNA） antibodies resistance index changes， traditional Chinese medicine （TCM） syndrome integral changes， and changes in serum cytokine indexes， blood rheology indexes， and T lymphocyte subsets indexes were observed. SLE changes in disease activity index （SLEDAI-2000）， quality of life （SF-36） scores， and adverse reactions were explored. ResultThe total effective rate was 96.08% （49/51） in the observation group， higher than 84.31% （43/51） in the control group （χ2=3.991， P<0.05）. The onset time， symptom improvement time， skin lesion regression time， and hospital stays in the observation group were shorter than those in the control group （P<0.05，P<0.01）. Before treatment， erythrocyte sedimentation rate （ESR）， platelet count （PLT）， hemoglobin （HGB）， white blood cell count （WBC）， and other blood routine indexes， 24h urinary protein levels， anti-ds-DNA， TCM syndrome integral core， serum cytokine indexes including interleukin-4 （IL-4）， IL-6， soluble interleukin-2 receptor （sIL-2R）， blood rheology indexes （fibrinogen， plasma viscosity， and whole blood viscosity），T lymphocyte subsets indexes （CD4+， CD8+， and CD4+/CD8+）， SLEDAI-2000， and SF-36 score comparison in both groups had no statistical significance. After treatment， the above indicators were improved in each group （P<0.05）， and the indicators in the observation group was better than that in the control group （P<0.05）. In terms of the adverse reactions， there was 1 case of digestive tract reaction， 1 case of elevated aminotransferase， and 1 case of insomnia in the observation group. There were 2 cases of digestive tract reaction，1 case of infection， and 1 case of elevated transaminase in the control group. The difference of the adverse reactions between the two groups had no statistical significance. ConclusionXijiao Dihuangtang combined with acupuncture has good clinical effect on the treatment of SLE with syndrome of intense heat toxin， and the method is safe， reliable， and worthy of application.

Mori Folium Improves Glucose and Lipid Metabolism Disorders in Rats with Type 2 Diabetes Mellitus by Regulating PI3K/Akt/PPARα/CPT-1 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg-1） group， and a Mori Folium water extract （4.0 g·kg-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.

Advances in drugs on targeting SMN2 for the treatment of spinal muscular atrophy / 药学学报

As one of the most serious hereditary neuromuscular disease, spinal muscular atrophy (SMA) is caused by the loss or mutation of survival motor neuron 1 (SMN1) gene. It leads to a decrease in the level of SMN protein and a consequent loss of alpha neurons and progressive muscle atrophy resulting in the progressive muscle weakness, the significant disability and the shortened lifespan. Up till now, only three drugs have been approved for SMA, including the gene therapy drug onasemnogene abeparvovec. The antisense oligonucleotide drug nusinersen and and the small molecule chemical drug risdiplam were briefly introduced. Some representative samples of the small molecule chemical drugs and antisense oligonucleotide drugs targeting SMN2 in the clinical trial or preclinical research phases were also reviewed.

Involvement of lncRNA IL21-AS1 in interleukin-2 and T follicular regulatory cell activation in systemic lupus erythematosus.

BACKGROUND: The single nucleotide polymorphism (SNP) rs62324212, located in IL21 antisense RNA 1 (IL21-AS1), has been identified as a genetic risk variant associated with systemic lupus erythematosus (SLE). We aimed to probe the characteristics of IL21-AS1 and explore its clinical relevance focusing on T helper subsets and disease activity in patients with SLE. METHODS: rs62324212 genotyping was determined using allelic discrimination by quantitative PCR. Gene expression in peripheral blood mononuclear cells and cell surface markers in CD4+ T cells were analyzed using PCR and flow cytometry. The association among IL21-AS1, CD4+ T cell subsets, and SLE disease activity was accessed. RESULTS: Ensembl Genome Browser analysis revealed that rs62324212 (C>A) was located in the predicting enhancer region of IL21-AS1. IL21-AS1 was expressed in the nucleus of CD4+ T and B cells, but its expression was decreased in patients with SLE. IL21-AS1 expression was positively correlated with mRNA levels of IL-2 but not IL-21, and it was associated with the proportion of activated T follicular regulatory (Tfr) cells. Furthermore, we observed a significant negative correlation between IL21-AS1 expression and disease activity in patients with SLE (n = 53, p < 0.05). CONCLUSION: IL21-AS1 has an effect on disease activity through an involvement of IL-2-mediated activation of Tfr cells in SLE. Thus, targeting the IL21-AS1 may provide therapeutic approaches for SLE.

Paraffin-Enabled Compressive Folding of Two-Dimensional Materials with Controllable Broadening of the Electronic Band Gap.

The capability to manipulate the size of the electronic band gap is of importance to semiconductor technology. Among these, a wide direct band gap is particularly helpful in optoelectronic devices due to the efficient utilization of blue and ultraviolet light. Here, we reported a paraffin-enabled compressive folding (PCF) strategy to widen the band gap of two-dimensional (2D) materials. Due to the large thermal expansion coefficient of paraffin, folded 2D materials can be achieved via thermal engineering of the paraffin-assisted transfer process. It can controllably introduce 0.2-1.3% compressive strain onto folded structures depending on the temperature differences and transfer the folding product to both rigid and soft substrates. Exemplified by MoS2, its folded multilayers demonstrated blue-shifts at direct gap transition peaks, six times stronger photoluminescence intensity, almost double mobility, and 20 times higher photoresponsivity over unfolded MoS2. This PCF strategy can attain controllable widening band gap of 2D materials, which will open up novel applications in optoelectronics.

Optimized adaptive Savitzky-Golay filtering algorithm based on deep learning network for absorption spectroscopy.

An improved Savitzky-Golay (S-G) filtering algorithm was developed to denoise the absorption spectroscopy of nitrogen oxide (NO2). A deep learning (DL) network was introduced to the traditional S-G filtering algorithm to adjust the window size and polynomial order in real time. The self-adjusting and follow-up actions of DL network can effectively solve the blindness of selecting the input filter parameters in digital signal processing. The developed adaptive S-G filter algorithm is compared with the multi-signal averaging filtering (MAF) algorithm to demonstrate its performance. The optimized S-G filtering algorithm is used to detect NO2 in a mid-quantum-cascade-laser (QCL) based gas sensor system. A sensitivity enhancement factor of 5 is obtained, indicating that the newly developed algorithm can generate a high-quality gas absorption spectrum for applications such as atmospheric environmental monitoring and exhaled breath detection.

Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases.

T follicular helper cells participate in stimulating germinal center (GC) formation and supporting B cell differentiation and autoantibody production. However, T follicular regulatory (Tfr) cells suppress B cell activation. Since changes in the number and functions of Tfr cells lead to dysregulated GC reaction and autoantibody response, targeting Tfr cells may benefit the treatment of autoimmune diseases. Differentiation of Tfr cells is a multistage and multifactorial process with various positive and negative regulators. Therefore, understanding the signals regulating Tfr cell generation is crucial for the development of targeted therapies. In this review, we discuss recent studies that have elucidated the roles of Tfr cells in autoimmune diseases and investigated the modulators of Tfr cell differentiation. Additionally, potential immunotherapies targeting Tfr cells are highlighted.