Inflammatory biomarkers in polymyositis/dermatomyositis patients with interstitial lung disease: a retrospective study.

BACKGROUND: Dermatomyositis (DM)/polymyositis (PM) is a systemic autoimmune disease characterized by proximal limb muscle with high morbidity and mortality and poor prognosis mediated by immune dysfunction; its etiology is unknown. DM/PM patients are at excessive risk of interstitial lung disease (ILD) and a higher risk of death. However, the role of circulating lymphocyte subsets, which play a pivotal role in occurrence and progression of DM/PM and ILD, respectively, remains unclear in DM/PM patients with ILD. METHODS: Demographic characteristics, general data, and peripheral lymphocyte levels measured by flow cytometry were collected and analyzed in 47 DM/PM patients with ILD, 65 patients without ILD, and 105 healthy controls (HCs). RESULTS: The most important first symptom of DM/PM patients is rash. Compared with non-ILD patients, the levels of neutrophil/lymphocyte ratio (NLR), systemic inflammatory response index (SIRI) were significantly higher and the levels of C reactive protein (CRP) were significantly lower in patients with ILD. Compared with HCs, DM/PM patients, with or without ILD, had decreased absolute counts of T, CD4 + T, CD8 + T, natural killer (NK), helper T (Th) 1, Th2, Th17, and regulatory T (Treg)cells. The fewest Th1 and Treg cells and the the lowest CD8 + T and Th1 cells percentages were seen in peripheral blood of patients with ILD. Longer duration, decreased lymphocyte/monocyte ratio (LMR)levels and CD8 + T and Th1 cells proportions, and fewer circulating Treg cells were independent risk factors for DM/PM with ILD. CONCLUSIONS: The identification of peripheral blood T lymphocyte subsets, especially Treg cells, and blood count in DM/PM appears to be useful in the comprehensive assessment of clinical lung involvement.

Cation-Intercalated Clay-Based Two-Dimensional Membranes for Effective Desalination and Molecule Sieving.

Montmorillonite (MMT) is known as an ion-exchangeable material, and cations between MMT nanosheets are easily exchanged by other cations. In this work, Ca2+, Fe3+, and Al3+ intercalated two-dimensional MMT membranes were developed by ion exchange of pristine MMT membranes (Na+-MMT), and their ion and dye removal abilities were investigated. The d-spacings of hydrated Fe3+ intercalated MMT membrane (Fe3+-MMT) and Al3+ intercalated MMT membrane (Al3+-MMT) were decreased compared with hydrated Na+-MMT membrane due to the stronger electrostatic attraction between Fe3+/Al3+ and negatively charged MMT nanosheets. Ion and dye sieving performances were improved significantly after the intercalation of Ca2+, Fe3+, and Al3+ into MMT membranes. Al3+-MMT membrane with a thickness of 1.17 µm could exclude 94% of Na+, and its ion sieving performance remained stable during a 120-h ion sieving experiment. Moreover, the rejection rate for rhodamine B (RB) reached 94% using an Al3+-MMT membrane with a thickness of 500 nm, and a water permeance of 73 L m-2 h-1 bar-1 was achieved. The excellent ion and dye sieving performances make it promising in the application of desalination and nanofiltration.

[Evaluation of the effect of secondary functional impression complete denture on improving oral health of edentulous patients].

PURPOSE: To evaluate the clinical effect of complete denture restoration in edentulous patients using secondary functional impression. METHODS: Complete denture restoration was performed in 433 edentulous patients using secondary functional impression. The Geriatric Oral Health Assessment Index (GOHAI) was used to evaluate patients' oral health-related quality of life before and after restoration. All patients were divided into 3 groups according to whether they had a history of denture restoration: no denture group(ND)，removable partial denture group(RPD), complete denture group(CD). In CD group, 30 patients were asked to chew two-colour gum. The SDhue value was evaluated by using ViewGum software. SPSS 26.0 software package was used for data analysis. RESULTS: The oral health-related quality of life was improved in all the 3 groups after restoration, and the GOHAI index 1 month after restoration was significantly higher than that before restoration(P＜0.05). In CD group, SDHue value of 30 patients after restoration was significantly lower than that before restoration(P＜0.05). CONCLUSIONS: Secondary functional impression is simple and fast, and can improve the satisfaction of patients after complete denture restoration.

The potential mechanism of the progression from latent to active tuberculosis based on the intestinal microbiota alterations.

INTRODUCTION: Tuberculosis (TB) poses a serious challenge to global health systems. The altered intestinal microbiota is associated with the pathogenesis of TB, but the exact links remain unclear. METHODS: 16 S rDNA sequencing was performed to comprehensively detect the changes in the intestinal microbiota of feces from active TB (ATB), latent TB infection (LTBI) and healthy controls (HC). RESULTS: The rarefaction curves demonstrated the sequencing results' validity. The alpha diversity was lowest in ATB, while highest in HC. Boxplot of beta diversity showed significant differences in every two groups. LDA Effect Size (LEfSe) Analysis revealed differences in probiotic bacteria like Romboutsia, Bifidobacterium and Lactobacillus in LTBI, and pro-inflammatory bacteria like R. gnavus, Streptococcus and Erysipelatoclostridium in ATB, corresponding to the cluster analysis. PICRUST2 analysis revealed the pentose phosphate pathway was active in ATB and LTBI (more active in ATB). The differences between the groups are statistically significant at the P<0.05 level. CONCLUSION: Our study indicated that from LTBI to ATB, some intestinal microbiota inhibit the synthesis of interferon (INF)-γ and interleukin (IL)-17, promoting the survival and spread of Mycobacterium tuberculosis (M. tb). In addition, the metabolites secreted by intestinal microbiota and dysbiosis in intestine also have an effect on the development of LTBI to ATB.

Untargeted Metabolomics of Feces Reveals Diagnostic and Prognostic Biomarkers for Active Tuberculosis and Latent Tuberculosis Infection: Potential Application for Precise and Non-Invasive Identification.

Purpose: Distinguishing latent tuberculosis infection (LTBI) from active tuberculosis (ATB) is important to control the prevalence of tuberculosis; however, there is currently no effective method. The aim of this study was to discover specific metabolites through fecal untargeted metabolomics to discriminate ATB, individuals with LTBI, and healthy controls (HC) and to probe the metabolic perturbation associated with the progression of tuberculosis. Patients and Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to comprehensively detect compounds in fecal samples from HC, LTBI, and ATB patients. Differential metabolites between the two groups were screened, and their underlying biological functions were explored. Candidate metabolites were selected and enrolled in LASSO regression analysis to construct diagnostic signatures for discriminating between HC, LTBI, and ATB. A receiver operating characteristic (ROC) curve was applied to evaluate diagnostic value. A nomogram was constructed to predict the risk of progression of LTBI. Results: A total of 35 metabolites were found to exist differentially in HC, LTBI, and ATB, and eight biomarkers were selected. Three diagnostic signatures based on the eight biomarkers were constructed to distinguish between HC, LTBI, and ATB, demonstrating excellent discrimination performance in ROC analysis. A nomogram was successfully constructed to evaluate the risk of progression of LTBI to ATB. Moreover, 3,4-dimethylbenzoic acid has been shown to distinguish ATB patients with different responses to etiological tests. Conclusion: This study constructed diagnostic signatures based on fecal metabolic biomarkers that effectively discriminated HC, LTBI, and ATB, and established a predictive model to evaluate the risk of progression of LTBI to ATB. The results provide scientific evidence for establishing an accurate, sensitive, and noninvasive differential diagnosis scheme for tuberculosis.

Combination of Bacillus and Low Fertigation Input Promoted the Growth and Productivity of Chinese Cabbage and Enriched Beneficial Rhizosphere Bacteria Lechevalieria.

Long-term overfertilization increases soil salinity and disease occurrence and reduces crop yield. Integrated application of microbial agents with low fertigation input might be a sustainable and cost-effective strategy. Herein, the promoting effects of Bacillus velezensis B006 on the growth of Chinese cabbage under different fertigation conditions in field trials were studied and the underlying mechanisms were revealed. In comparison with normal fertigation (water potential of -30 kPa and soluble N, P, K of 29.75, 8.26, 21.48 Kg hm-2) without B006 application, the combination of B. velezensis B006 and reduced fertigation input (-50 kPa and N, P, K of 11.75, 3.26, 6.48 Kg hm-2) promoted cabbage growth and root development, restrained the occurrence of soft rot disease, and improved the yield. High-performance liquid chromatography (HPLC) analyses indicated that B006 application promoted the production of indole-3-acetic acid and salicylic acid in cabbage roots, which are closely related to plant growth. Rhizosphere microbiota analyses indicated that the combination of low fertigation input and B006 application promoted the enrichment of Streptomyces, Lechevalieria, Promicromonospora, and Aeromicrobium and the abundance of Lechevalieria was positively correlated with the root length and vitality. This suggested that the integrated application of reduced fertigation and Bacillus is highly efficient to improve soil ecology and productivity and will benefit the sustainable development of crop cultivation in a cost-effective way.

Effects of tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer.

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.

Design, synthesis, activity and molecular dynamics studies of 1,3,4-thiadiazole derivatives as selective allosteric inhibitors of SHP2 for the treatment of cancer.

Overexpression or gene mutation of SHP2 is closely linked with a variety of cancers and has been identified as a crucial anticancer target. In the study, we took SHP2 allosteric inhibitor SHP099 as the lead compound, and 32 1,3,4-thiadiazole derivatives were identified as selective allosteric inhibitors of SHP2. In vitro enzyme activity test showed that some compounds had high inhibition on full length SHP2, and almost no activity on homologous protein SHP1, exhibiting high selectivity. Compound YF704 (4w) had the best inhibition activity, with IC50 value of 0.25 ± 0.02 µM, and also showed strong inhibitory activity on SHP2-E76K and SHP2-E76A, with IC50 values of 6.88 ± 0.69 µM and 1.38 ± 0.12 µM, respectively. CCK8 proliferation test found that multiple compounds would effectively inhibit the proliferation of a variety of cancer cells. Among them, the IC50 values of compound YF704 on MV4-11 and NCI-H358 cells were 3.85 ± 0.34 µM and 12.01 ± 0.62 µM, respectively. Specially, these compounds were sensitive to NCI-H358 cells containing KRASG12C mutation, thus overcoming the problem that SHP099 was insensitive to such cells. Apoptosis experiment showed that compound YF704 would effectively induce apoptosis of MV4-11 cells. Western blot showed that compound YF704 would downregulate the phosphorylation levels of Erk1/2 and Akt in MV4-11 and NCI-H358 cells. Molecular docking study show that compound YF704 would effectively bind to the allosteric region of SHP2 and form hydrogen bond interactions with key residues Thr108, Arg111 and Phe113. Molecular dynamics study further revealed the binding mechanism of SHP2 and compound YF704. In conclusion, we hope to provide potential SHP2 selective inhibitors and provide valuable clues for cancer treatment.

Identification of natural product inhibitors of PTP1B based on high-throughput virtual screening strategy: In silico, in vitro and in vivo studies.

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathway, which is a potential therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). In this study, we identified several PTP1B inhibitors with high activity by using high-throughput virtual screening and in vitro enzyme inhibition activity verification strategies. Among them, baicalin was first reported as a selective mixed inhibitor of PTP1B, with IC50 value of 3.87 ± 0.45 µM, and its inhibitory activity against homologous proteins TCPTP, SHP2, and SHP1 exceeded 50 µM. Molecular docking study found that baicalin and PTP1B could bind stably, and revealed that baicalin had a dual inhibitory effect. Cell experiments showed that baicalin was almost non-toxic and could significantly enhance the phosphorylation of IRS-1 in C2C12 myotube cells. Animal experiments showed that baicalin could significantly reduce the blood sugar of STZ-induced diabetic mice models, and had a liver protective effect. In conclusion, this study can provide new ideas for the development of PTP1B selective inhibitors.

Distribution characteristics of oral microbiota and its relationship with intestinal microbiota in patients with type 2 diabetes mellitus.

Introduction: Type 2 diabetes mellitus (T2DM) has a high incidence rate globally, increasing the burden of death, disability, and the economy worldwide. Previous studies have found that the compositions of oral and intestinal microbiota changed respectively in T2DM; whether the changes were associated or interacted between the two sites and whether there were some associations between T2DM and the ectopic colonization of oral microbiota in the gut still need to be identified. Research design and methods: We performed a cross-sectional observational study; 183 diabetes and 74 controls were enrolled. We used high-throughput sequencing technology to detect the V3-V4 region of 16S rRNA in oral and stool samples. The Source Tracker method was used to identify the proportion of the intestinal microbiota that ectopic colonized from the oral cavity. Results: The oral marker bacteria of T2DM were found, such as Actinobacteria, Streptococcus, Rothia, and the intestinal marker bacteria were Bifidobacterium, Streptococcus, and Blautia at the genus level. Among them, Actinobacteria and Blautia played a vital role in different symbiotic relationships of oral and intestinal microbiota. The commonly distributed bacteria, such as Firmicutes, Bacteroidetes, and Actinobacteria, were found in both oral and intestine. Moreover, the relative abundance and composition of bacteria were different between the two sites. The glycine betaine degradation I pathway was the significantly up-regulated pathway in the oral and intestinal flora of T2DM. The main serum indexes related to oral and intestinal flora were inflammatory. The relative abundance of Proteobacteria in the intestine and the Spirochete in oral was positively correlated, and the correlation coefficient was the highest, was 0.240 (P<0.01). The proportion of ectopic colonization of oral flora in the gut of T2DM was 2.36%. Conclusion: The dysbacteriosis exited in the oral and intestine simultaneously, and there were differences and connections in the flora composition at the two sites in T2DM. Ectopic colonization of oral flora in the intestine might relate to T2DM. Further, clarifying the oral-gut-transmitting bacteria can provide an essential reference for diagnosing and treating T2DM in the future.

Salt-blocking three-dimensional Janus evaporator with superwettability gradient for efficient and stable solar desalination.

Solar interfacial steam power generation is a prospective method for seawater desalination. In this work, a salt-blocking three-dimensional (3D) Janus evaporator with a superhydrophobic to superhydrophilic gradient was fabricated by spraying a composite dispersion of multi-walled carbon nanotubes/polydimethylsiloxane (CNTs/PDMS) onto the top side of a polyurethane (PU) foam and polyvinyl alcohol (PVA) solution onto the bottom side. The CNTs/PDMS composite dispersion with nanostructured CNTs and low surface energy PDMS combined with the porous structure of the PU foam rendered the top side superhydrophobic. Therefore, a layer suitable for photothermal conversion was obtained. The hydrophilic PVA combined with the porous structure of the foam rendered the bottom side superhydrophilic, facilitating water absorption and transportation. The asymmetric wettability gradient of the CNTs/PDMS-PU-PVA as a 3D evaporator caused the evaporation rate and transportation speed of water to reach a balance, and the salt was quickly dissolved at the superhydrophilic interface. This 3D salt-resistant Janus evaporator achieved an evaporation rate of 2.26 kg m-2 h-1 under 1 kW m-2 illumination.

Characteristics of recurrence, predictors for relapse and prognosis of rapid relapse triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) patients who recur at different times are associated with distinct biological characteristics and prognoses. Research on rapid-relapse TNBC (RR-TNBC) is sparse. In this study, we aimed to describe the characteristics of recurrence, predictors for relapse, and prognosis in rrTNBC patients. Methods: Clinicopathological data of 1584 TNBC patients from 2014 to 2016 were retrospectively reviewed. The characteristics of recurrence were compared between patients with RR-TNBC and slow relapse TNBC(SR-TNBC). All TNBC patients were randomly divided into a training set and a validation set to find predictors for rapid relapse. The multivariate logistic regression model was used to analyze the data of the training set. C-index and brier score analysis for predicting rapid relapse in the validation set was used to evaluate the discrimination and accuracy of the multivariate logistic model. Prognostic measurements were analyzed in all TNBC patients. Results: Compared with SR-TNBC patients, RR-TNBC patients tended to have a higher T staging, N staging, TNM staging, and low expression of stromal tumor-infiltrating lymphocytes (sTILs). The recurring characteristics were prone to appear as distant metastasis at the first relapse. The first metastatic site was apt to visceral metastasis and less likely to have chest wall or regional lymph node metastasis. Six predictors (postmenopausal status, metaplastic breast cancer,≥pT3 staging,≥pN1 staging, sTIL intermediate/high expression, and Her2 [1+]) were used to construct the predictive model of rapid relapse in TNBC patients. The C-index and brier score in the validation set was 0.861 and 0.095, respectively. This suggested that the predictive model had high discrimination and accuracy. The prognostic data for all TNBC patients showed that RR-TNBC patients had the worst prognosis, followed by SR-TNBC patients. Conclusion: RR-TNBC patients were associated with unique biological characteristics and worse outcomes compared to non-RR-TNBC patients.

The Co-Association of Enterobacteriaceae and Pseudomonas with Specific Resistant Cucumber against Fusarium Wilt Disease.

The root microbiota contributes to the plant's defense against stresses and pathogens. However, the co-association pattern of functional bacteria that improves plant resistance has not been interpreted clearly. Using Illumina high-throughput sequencing technology, the root bacterial community profiles of six cucumber cultivars with different resistance in response to the causative agent of cucumber Fusarium wilt (CFW), Fusarium oxysporum f. sp. cucumerinum (Foc), were analyzed. The principal coordinate analysis indicated that the interactions of the cultivars and pathogens drove the cucumber root bacterial communities (p = 0.001). The resistance-specific differential genera across the cultivars were identified, including Massilia in the resistant cultivars, unclassified Enterobacteriaceae in resistant CL11 and JY409, Pseudomonas in JY409, Cronobacter in moderately resistant ZN106, and unclassified Rhizobiaceae and Streptomyces in susceptible ZN6. The predominant root bacterium Massilia accounted for the relative abundance of up to 28.08-61.55%, but dramatically declined to 9.36% in Foc-inoculated susceptible ZN6. Pseudomonas ASV103 and ASV48 of Pseudomonadaceae and Cronobacter ASV162 of Enterobacteriaceae were consistently differential across the cultivars at the phylum, genus, and ASV levels. Using the culture-based method, antagonistic strains of Enterobacteriaceae with a high proportion of 51% were isolated. Furthermore, the bacterial complexes of Pantoea dispersa E318 + Pseudomonas koreensis Ps213 and Cronobacter spp. C1 + C7 reduced the disease index of CFW by 77.2% and 60.0% in the pot experiment, respectively. This study reveals the co-association of specific root bacteria with host plants and reveals insight into the suppressing mechanism of resistant cultivars against CFW disease by regulating the root microbiota.

Scalable and Mechanically Durable Superhydrophobic Coating of SiO2/Polydimethylsiloxane/Epoxy Nanocomposite.

The mechanical durability of superhydrophobic surfaces is of significance for their practical applications. However, few reports about superhydrophobic coating on certain substrates took into consideration both the mechanical stability of the superhydrophobic coating and adhesion stability between the coating and the substrate. Herein, we put forward a facile and efficient strategy to construct robust superhydrophobic coatings by simply spray-coating a composite suspension of SiO2 nanoparticles, polydimethylsiloxane (PDMS), and epoxy resin (EP) on substrates pretreated with an EP base-coating. The as-obtained coating exhibited excellent superhydrophobicity with water contact angle of 163° and sliding angle of 3.5°, which could endure UV irradiation of 180 h, immersion in acidic or basic solutions for 168 h, and outdoor exposure for over 30 days. Notably, the coating surface retained superhydrophobicity after being successively impacted with faucet water for 1 h, impinged with 360 g sand grains, and abraded with sandpaper of 120 grid under a load of 500 g for 5 m distance. The outstanding mechanical stability was mainly attributed to the cross-linking of EP and the elastic nature of PDMS which ensured strong cohesion inside the whole coating and to the substrate. Additionally, the coating showed self-healing capacity against O2 plasma etching. The method is simple with the materials commercially available and is expected to be widely applied in outdoor applications.

Superhydrophobic Porous Coating of Polymer Composite for Scalable and Durable Daytime Radiative Cooling.

Passive daytime radiative cooling (PDRC) technology provides an eco-friendly cooling strategy by reflecting sunlight reaching the surface and radiating heat underneath to the outer space through the atmospheric transparency window. However, PDRC materials face challenges in cooling performance degradation caused by outdoor contamination and requirements of easy fabrication approaches for scale-up and high cooling efficiency. Herein, a polymer composite coating of polystyrene, polydimethylsiloxane and poly(ethyl cyanoacrylate) (PS/PDMS/PECA) with superhydrophobicity and radiative cooling performance was fabricated and demonstrated to have sustained radiative cooling capability, utilizing the superhydrophobic self-cleaning property to maintain the optical properties of the coating surface. The prepared coating is hierarchically porous which exhibits an average solar reflectance of 96% with an average emissivity of 95% and superhydrophobicity with a contact angle of 160°. The coating realized a subambient radiative cooling of 12.9 °C in sealed air and 7.5 °C in open air. The self-cleaning property of the PS/PDMS/PECA coating helped sustain the cooling capacity for long-term outdoor applications. Moreover, the coating exhibited chemical resistance, UV resistance, and mechanical durability, which has promising applications in wider fields.

STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression.

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.

Identification of the novel natural product inhibitors of SHP2 from the plant Toona sinensis: In vitro and in silico study.

In this study, we tested the inhibitory activity of 45 natural products extracted from the plant Toona sinensis on SHP2 protein, and identified four natural product inhibitors. The natural product 1,2,3,6-Tetragalloylglucose (A-1) was first reported as a competitive inhibitor of SHP2, with an IC50 value of 0.20 ± 0.029 µM and the selectivity of 1.8-fold and 4.35-fold to high homologous proteins SHP1 and PTP1B, respectively. Compound A-1 also showed high inhibitory activity on SHP2-E76K and SHP2-E76A mutants, with IC50 values of 0.95 ± 0.21 µM and 0.29 ± 0.045 µM, respectively. Cell viability assay showed that compound A-1 could inhibit the proliferation of a variety of cancer cells. Apoptosis assay showed that compound A-1 could effectively induce apoptosis of KRASG12C-mut NCI-H23 and KRASG12S-mut A549 cells. Western blot assay showed that compound A-1 could down regulate the phosphorylation levels of Erk1/2 and Akt in NCI-H23 and A549 cells. Molecular docking showed that compound A-1 could effectively dock to the catalytic active region of SHP2. Molecular dynamics simulation explored the effect of compound A-1 on SHP2, revealing the deep-seated binding mechanism. This study would provide valuable clues for the development of SHP2 and its mutant inhibitors.

The prevalence and characteristics of alexithymia in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Alexithymia is common in patients with type 2 diabetes mellitus (T2DM). Although the estimated prevalence of alexithymia in patients with T2DM is widely reported, these results have not been synthesized. AIM: To systematically assess the prevalence and characteristics of alexithymia in patients with T2DM. METHODS: We searched for relevant publications in PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database, and Weipu Database. The prevalence of alexithymia, the mean scores, and standard deviations of the total scale of the 20-item Toronto Alexithymia Scale (TAS-20) were pooled using random effects meta-analysis in Stata 13.0, with studies stratified by study location in this meta-analysis. RESULTS: This meta-analysis included thirteen articles. Pooled prevalence of alexithymia (TAS-20 total scores ≥61) were 43.0% (95%CI 35.0-51.0%), and the prevalence of alexithymia was higher in China (45.0%, 95%CI 36.0-54.0%) compared with non-China (41.0%, 95%CI 29.0-54.0%). The pooled mean score for the TAS-20 total scale was 57.70 (95% CI 55.25-60.15). Leave-one-out analysis showed that none of the studies significantly impacted the overall pooled results. CONCLUSIONS: This meta-analysis indicated a high prevalence of alexithymia in patients with T2DM. Thus, clinicians need to be aware of and assess appropriately for alexithymia in patients with T2DM.

SP1 Promotes HDAC4 Expression and Inhibits HMGB1 Expression to Reduce Intestinal Barrier Dysfunction, Oxidative Stress, and Inflammatory Response after Sepsis.

As a serious and elusive syndrome caused by infection, sepsis causes a high rate of mortality around the world. Our investigation aims at exploring the role and possible mechanism of specificity protein-1 (SP1) in the development of sepsis. A mouse model of sepsis was established by cecal ligation perforation, and a cellular model was stimulated by lipopolysaccharide (LPS), followed by determination of the SP1 expression. It was determined that SP1 was poorly expressed in the intestinal tissues of septic mice and LPS-treated cells. Next, we examined the interactions among SP1, histone deacetylase 4 (HDAC4), and high mobility group box 1 (HMGB1) and found that SP1 bound to the HDAC4 promoter to upregulate its expression, thereby promoting the deacetylation of HMGB1. Meanwhile, gain- or loss-of-function approaches were applied to evaluate the intestinal barrier dysfunction, oxidative stress, and inflammatory response. Overexpression of SP1 or underexpression of HMGB1 was observed to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory injury. Collectively, these experimental data provide evidence reporting that SP1 could promote the HDAC4-mediated HMGB1 deacetylation to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory response induced by sepsis, providing a novel therapeutic target for sepsis prevention and treatment.

A Superhydrophobic Dual-Mode Film for Energy-Free Radiative Cooling and Solar Heating.

Traditional electric cooling in summer and coal heating in winter consume a huge amount of energy and lead to a greenhouse effect. Herein, we developed an energy-free dual-mode superhydrophobic film, which consists of a white side with porous coating of styrene-ethylene-butylene-styrene/SiO2 for radiative cooling and a black side with nanocomposite coating of carbon nanotubes/polydimethylsiloxane for solar heating. In the cooling mode with the white side, the film achieved a high sunlight reflection of 94% and a strong long-wave infrared emission of 92% in the range of 8-13 µm to contribute to a temperature drop of ∼11 °C. In the heating mode with the black side, the film achieved a high solar absorption of 98% to induce heating to raise the air temperature beneath by ΔT of ∼35.6 °C. Importantly, both sides of the film are superhydrophobic with a contact angle over 165° and a sliding angle near 0°, showing typical self-cleaning effects, which defend the surfaces from outdoor contamination, thus conducive to long-term cooling and heating. This dual-mode film shows great potential in outdoor applications as coverings for both cooling in hot summer and heating in winter without an energy input.