Conserved methylation signatures associate with the tumor immune microenvironment and immunotherapy response.

BACKGROUND: Aberrant DNA methylation is a major characteristic of cancer genomes. It remains unclear which biological processes determine epigenetic reprogramming and how these processes influence the variants in the cancer methylome, which can further impact cancer phenotypes. METHODS: We performed pairwise permutations of 381,900 loci in 569 paired DNA methylation profiles of cancer tissue and matched normal tissue from The Cancer Genome Atlas (TCGA) and defined conserved differentially methylated positions (DMPs) based on the resulting null distribution. Then, we derived independent methylation signatures from 2,465 cancer-only methylation profiles from the TCGA and 241 cell line-based methylation profiles from the Genomics of Drug Sensitivity in Cancer (GDSC) cohort using nonnegative matrix factorization (NMF). We correlated DNA methylation signatures with various clinical and biological features, including age, survival, cancer stage, tumor immune microenvironment factors, and immunotherapy response. We inferred the determinant genes of these methylation signatures by integrating genomic and transcriptomic data and evaluated the impact of these signatures on cancer phenotypes in independent bulk and single-cell RNA/methylome cohorts. RESULTS: We identified 7,364 differentially methylated positions (2,969 Hyper-DMPs and 4,395 Hypo-DMPs) in nine cancer types from the TCGA. We subsequently retrieved three highly conserved, independent methylation signatures (Hyper-MS1, Hypo-MS1, and Hypo-MS4) from cancer tissues and cell lines based on these Hyper and Hypo-DMPs. Our data suggested that Hypo-MS4 activity predicts poor survival and is associated with immunotherapy response and distant tumor metastasis, and Hypo-MS4 activity is related to TP53 mutation and FOXA1 binding specificity. In addition, we demonstrated a correlation between the activities of Hypo-MS4 in cancer cells and the fractions of regulatory CD4 + T cells with the expression levels of immunological genes in the tumor immune microenvironment. CONCLUSIONS: Our findings demonstrated that the methylation signatures of distinct biological processes are associated with immune activity in the cancer microenvironment and predict immunotherapy response.

Uncovering the Recent Progress of CNC-Derived Chirality Nanomaterials: Structure and Functions.

Cellulose nanocrystal (CNC), as a renewable resource, with excellent mechanical performance, low thermal expansion coefficient, and unique optical performance, is becoming a novel candidate for the development of smart material. Herein, the recent progress of CNC-based chirality nanomaterials is uncovered, mainly covering structure regulations and function design. Undergoing a simple evaporation process, the cellulose nanorods can spontaneously assemble into chiral nematic films, accompanied by a vivid structural color. Various film structure-controlling strategies, including assembly means, physical modulation, additive engineering, surface modification, geometric structure regulation, and external field optimization, are summarized in this work. The intrinsic correlation between structure and performance is emphasized. Next, the applications of CNC-based nanomaterials is systematically reviewed. Layer-by-layer stacking structure and unique optical activity endow the nanomaterials with wide applications in the mineralization, bone regeneration, and synthesis of mesoporous materials. Besides, the vivid structural color broadens the functions in anti-counterfeiting engineering, synthesis of the shape-memory and self-healing materials. Finally, the challenges for the CNC-based nanomaterials are proposed.

Pedal medial arterial calcification in diabetic foot ulcers: A significant risk factor of amputation and mortality.

AIMS: Pedal medial arterial calcification (MAC) is frequently observed in individuals with diabetic foot ulcers (DFUs). However, the impact of pedal MAC on individuals with DFUs remains uncertain. The main aim of this study was to evaluate the association between pedal MAC with amputation and mortality outcomes. METHODS: A prospective, observational cohort study was conducted at West China Hospital from January 2012 to December 2021. Logistic regression analyses, Kaplan-Meier survival method, and Cox proportional hazards models were employed to evaluate the relationship between pedal MAC and amputation as well as mortality. RESULTS: A total of 979 patients were enrolled in the study. Peripheral artery disease (PAD) was observed in 53% of patients with DFUs, and pedal MAC was found in 8%. Over a median follow-up of 46 (23-72) months, foot amputation was performed on 190 patients, and mortality occurred in 246 patients. Pedal MAC showed a significant association with amputation both in unadjusted analysis (odds ratio [OR] = 2.98, 95% confidence interval [CI] = 1.86-4.76, p < .001) and after adjusting sex, age, albumin levels, hemoglobin levels, and diabetic retinopathy status (OR 2.29, 95% CI 1.33-3.93, p = .003). The risk of amputation was found to be twofold higher in individuals with PAD and pedal MAC compared to those with PAD alone (OR 2.05, 95% CI 1.10-3.82, p = .024). Furthermore, the presence of pedal MAC was significantly associated with an increased risk of mortality (p = .005), particularly among individuals with DFUs but without PAD (HR 4.26, 95% CI 1.90-9.52, p < .001), rather than in individuals presenting with both DFUs and PAD. CONCLUSION: The presence of pedal MAC is significantly associated with both amputation and mortality in individuals with DFUs. Moreover, pedal MAC could provide additional value to predict amputation other than PAD.

Bifunctional Chiral Agent Enables One-pot Spontaneous Deracemization of Racemic Compounds.

A novel one-pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α-diphenyl-2-pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2R,3R)-enantiomer and (2S,3S)-enantiomer in solution, achieving a one-pot spontaneous deracemization. This strategy was also successfully extended to the deracemization of three other racemic compound drugs: (R,S)-carprofen, (R,S)-indoprofen, and (R,S)-indobufen. The one-pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization-induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy.

Growth "self-inhibition" of irbesartan desmotrope: surface intra-annular tautomer inter-conversion is the culprit.

The newly discovered growth self-inhibition phenomenon of tautomeric crystals is now generalized to the demostrope (form B) of irbesartan that displays intra-annular tautomerism in neutral aqueous solutions. The dynamic intra-annular tautomer inter-conversion on the surface is the key factor. Our findings provide implications for producing and engineering tautomeric materials.

FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer.

Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354-406 amino acids) to suppress the latter's ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8+ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25+ Foxp3+) and exhausted T cells (PD1+ CD8+), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.

How health risk factors affect inpatient costs among adults with stroke in China: the mediating role of length of stay.

BACKGROUND: As stroke has become the leading cause of death and disability in China, it has induced a heavy disease burden on society, families, and patients. Despite much attention within the literature, the effect of multiple risk factors on length of stay (LOS) and inpatient costs in China is still not fully understood. AIM: To analyse the association between the number of risk factors combined and inpatient costs among adults with stroke and explore the mediating effect of LOS on inpatient costs. METHODS: A retrospective cross-sectional study was conducted among stroke patients in a tertiary hospital in Nantong City from January 2018 to December 2019. Lifestyle factors (smoking status, exercise), personal disease history (overweight, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation), family history of stroke, and demographic characteristics were interviewed by trained nurses. Inpatient costs and LOS were extracted from electronic medical records. Hierarchical multiple linear regression models and mediation analysis were used to examine the direct and indirect effects of the number of risk factors combined for stroke on inpatient costs. RESULTS: A total of 620 individuals were included, comprising 391 ischaemic stroke patients and 229 haemorrhagic stroke patients, and the mean age was 63.2 years, with 60.32% being male. The overall mean cost for stroke inpatients was 30730.78 CNY ($ 4444.91), and the average length of stay (LOS) was 12.50 days. Mediation analysis indicated that the greater number of risk factors was not only directly related to higher inpatient costs (direct effect = 0.16, 95%CI:[0.11,0.22]), but also indirectly associated with inpatient cost through longer LOS (indirect effect = 0.08, 95% CI: [0.04,0.11]). Furthermore, patients with high risk of stroke had longer LOS than those in low-risk patients, which in turn led to heavier hospitalization expenses. CONCLUSIONS: Both the greater number of risk factors and high-risk rating among stroke patients increased the length of stay and inpatient costs. Preventing and controlling risk behaviors of stroke should be strengthened.

Fe-curcumin nanozyme-mediated immunosuppression and anti-inflammation in experimental autoimmune uveitis.

BACKGROUND: EAU is an inflammatory disease usually characterized by autoinflammation and autoimmunity and is aggravated by excessive generation of ROS. Conventional hormone therapy often has more adverse effects. It is urgent to find a therapeutic drug with higher efficiency and fewer adverse effects. METHODS: We developed an Fe-curcumin nanozyme in which natural antioxidants coordinate with Fe3+ to form nanoparticles with excellent solubility for directing anti-inflammatory and ROS scavenging effects to treat EAU. Several experiments were used to detect the characteristics of nanozymes. EAU model rats were used to detect the abilities of decreasing autoinflammation and autoimmunity. PBMCs were used to detect the ability to inhibit cell proliferation. RESULTS: Free radical scavenging experiments showed that nanozymes decreased the level of free radicals at low concentrations. In vitro and in vivo experiments revealed that the group treated with Fe-curcumin nanozymes had lower inflammatory reactions and ROS levels than the control group, as reflected by the downregulated levels of several critical inflammatory cytokines, such as IFN-γ, IL-17, and TNF-α; decreased H2O2 release; inhibited proliferation of Th1 and Th17 cells; and alleviated pathological changes in the eye. Importantly, the Fe-curcumin nanozyme was detected in the retina using Prussian blue staining. Additionally, Fe-curcumin nanozyme is noncytotoxic when directing these biological activities. CONCLUSION: This study has demonstrated the feasibility of using the Fe-curcumin nanozyme as a nanodrug to inhibit inflammatory reactions and scavenge ROS in the treatment of EAU, indicating that it may serve as a promising therapeutic agent in clinical treatment.

A multimodal pipeline for image correction and registration of mass spectrometry imaging with microscopy.

The integration of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and histology plays a pivotal role in advancing our understanding of complex heterogeneous tissues, which provides a comprehensive description of biological tissue with both wide molecule coverage and high lateral resolution. Herein, we proposed a novel strategy for the correction and registration of MALDI MSI data with hematoxylin & eosin (H&E) staining images. To overcome the challenges of discrepancies in spatial resolution towards the unification of the two imaging modalities, a deep learning-based interpolation algorithm for MALDI MSI data was constructed, which enables spatial coherence and the following orientation matching between images. Coupled with the affine transformation (AT) and the subsequent moving least squares algorithm, the two types of images from one rat brain tissue section were aligned automatically with high accuracy. Moreover, we demonstrated the practicality of the developed pipeline by projecting it to a rat cerebral ischemia-reperfusion injury model, which would help decipher the link between molecular metabolism and pathological interpretation towards microregion. This new approach offers the chance for other types of bioimaging to boost the field of multimodal image fusion.

Ginsenoside Rh1, a novel casein kinase II subunit alpha (CK2α) inhibitor, retards metastasis via disrupting HHEX/CCL20 signaling cascade involved in tumor cell extravasation across endothelial barrier.

Tumor cell extravasation across endothelial barrier has been recognized as a pivotal event in orchestrating metastasis formation. This event is initiated by the interactions of extravasating tumor cells with endothelial cells (ECs). Therefore, targeting the crosstalk between tumor cells and ECs might be a promising therapeutic strategy to prevent metastasis. In this study, we demonstrated that Rh1, one of the main ingredients of ginseng, hindered the invasion of breast cancer (BC) cells as well as diminished the permeability of ECs both in vitro and in vivo, which was responsible for the attenuated tumor cell extravasation across endothelium. Noteworthily, we showed that ECs were capable of inducing the epithelial-mesenchymal transition (EMT) and invadopodia of BC cells that are essential for tumor cell migration and invasion through limiting the nuclear translocation of hematopoietically expressed homeobox (HHEX). The decreased nuclear HHEX paved the way for initiating the CCL20/CCR6 signaling axis, which in turn contributed to damaged endothelial junctions, uncovering a new crosstalk mode between tumor cells and ECs. Intriguingly, Rh1 inhibited the kinase activity of casein kinase II subunit alpha (CK2α) and further promoted the nuclear translocation of HHEX in the BC cells, which resulted in the disrupted crosstalk between chemokine (C-C motif) ligand 20 (CCL20) in the BC cells and chemokine (C-C motif) receptor 6 (CCR6) in the ECs. The prohibited CCL20-CCR6 axis by Rh1 enhanced vascular integrity and diminished tumor cell motility. Taken together, our data suggest that Rh1 serves as an effective natural CK2α inhibitor that can be further optimized to be a therapeutic agent for reducing tumor cell extravasation.

Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma.

BACKGROUND: Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages. METHODS: In this investigation, immune cells isolated from surrounding normal tissues and cancer tissues from 3 II-stage and 4 III-stage HCC cases were subjected to deep scRNA-seq. The analysis included 15 samples. We distinguished developmentally relevant trajectories, unique immune cell subtypes, and enriched pathways regarding differential genes. Western blot and co-immunoprecipitation were performed to demonstrate the interaction between fatty acid binding protein 1 (FABP1) and peroxisome proliferator-activated receptor gamma(PPARG). In vivo experiments were performed in a C57BL/6 mouse model of HCC established via subcutaneous injection. RESULTS: FABP1 was discovered to be overexpressed in tumor-associated macrophages (TAMs) with III-stage HCC tissues compared with II-stage HCC tissues. This finding was fully supported by immunofluorescence detection in significant amounts of HCC human samples. FABP1 deficiency in TAMs inhibited HCC progression in vitro. Mechanistically, FABP1 interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. When compared with C57BL/6 mice of the wild type, tumors in FABP1-/- mice consistently showed attenuation. The FABP1-/- group's relative proportion of regulatory T cells and natural killer cells showed a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend, according to the results of mass cytometry. In further clinical translation, we found that orlistat significantly inhibited FABP1 activity, while the combination of anti-programmed cell death 1(PD-1) could synergistically treat HCC progression. Liposomes loaded with orlistat and connected with IR780 probe could further enhance the therapeutic effect of orlistat and visualize drug metabolism in vivo. CONCLUSIONS: ScRNA-seq atlas revealed an FABP1-dependent immunosuppressive environment in HCC. Orlistat significantly inhibited FABP1 activity, while the combination of anti-PD-1 could synergistically treat HCC progression. This study identified new treatment targets and strategies for HCC progression, contributing to patients with advanced HCC from new perspectives.

Prevalence and related factors of abdominal obesity among urban adults aged 35 to 79 years in southwest China.

Objectives: This study aimed to investigate the prevalence and related factors of abdominal obesity among urban adults aged 35 to 79 years in southwest China. Methods: From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,981 people aged 35-79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. Abdominal obesity was defined as waist circumference ≥ 90 cm for men and ≥ 85 cm for women. Results: The prevalence of abdominal obesity was 30.7%, 24.8% in males and 33.9% in females (p < 0.001). The prevalence of abdominal obesity increased with BMI. The prevalence of abdominal obesity was positively correlated with age, sex, marriage, alcohol consumption, hypertension and diabetes, and negatively correlated with high education level, smoking and Physical activity. Conclusion: The prevalence of abdominal obesity among adults aged 35-79 in urban communities in southwest China is high, which is close to that of adults in urban communities in China. We should strengthen health education among the population, adopt healthy diet, maintain moderate physical activity and other measures to curb the prevalence of abdominal obesity in urban communities in southwest China.

Development of an Efficient On-Tissue Epoxidation Reaction Mediated by Urea Hydrogen Peroxide for MALDI MS/MS Imaging of Lipid C═C Location Isomers.

Unsaturated lipids containing different numbers and locations of C═C bonds are significantly associated with a variety of cellular and metabolic functions. Although matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has been used to visualize the spatial distribution patterns of various lipids in biological tissues, in situ identification, discrimination, and visualization of lipid C═C location isomers remain challenging. Herein, an efficient and fast on-tissue chemical derivatization (OTCD) approach was developed to pinpoint the locations of C═C bonds in complex lipids in situ via methyltrioxorhenium (MTO)-catalyzed epoxidation of C═C with a urea hydrogen peroxide (UHP)/hexafluoroisopropanol (HFIP) system. The efficiency of OTCD could reach 100% via one-step spray deposition of the solution mixture of MTO/UHP/HFIP at room temperature. The developed OTCD method provided rich structural information on lipid C═C location isomers, and their accurate spatial distribution patterns were resolved in mouse brain tissues. Tissue-specific distributions and changes of lipid C═C location isomers in the liver sections of obese ob/ob and diabetic db/db mice were further investigated, and their correlation in two animal models was revealed. The simplicity and high efficiency of the OTCD method developed for MALDI tandem MSI of lipid C═C location isomers possess great potential for functional spatial lipidomics.

Chirality Supramolecular Systems: Helical Assemblies, Structure Designs, and Functions.

Chirality, as one of the most striking characteristics, exists at various scales in nature. Originating from the interactions of host and guest molecules, supramolecular chirality possesses huge potential in the design of functional materials. Here, an overview of the recent progress in structure designs and functions of chiral supramolecular materials is present. First, three design routes of the chiral supramolecular structure are summarized. Compared with the template-induced and chemical synthesis strategies that depend on accurate molecular identification, the twisted-assembly technique creates chiral materials through the ordered stacking of the nanowire or films. Next, chirality inversion and amplification are reviewed to explain the chirality transfer from the molecular level to the macroscopic scale, where the available external stimuli on the chirality inversion are also given. Lastly, owing to the optical activity and the characteristics of the layer-by-layer stacking structure, the supramolecular chirality materials display various excellent performances, including smart response, shape-memorization, superior mechanical performance, and applications in biomedical fields. To sum up, this work provides a systematic review of the helical assemblies, structure design, and applications of supramolecular chirality systems.

PELP1 inhibition by SMIP34 reduces endometrial cancer progression via attenuation of ribosomal biogenesis.

Endometrial carcinoma (ECa) is the fourth most common cancer among women. The oncogene PELP1 is frequently overexpressed in a variety of cancers, including ECa. We recently generated SMIP34, a small-molecule inhibitor of PELP1 that suppresses PELP1 oncogenic signaling. In this study, we assessed the effectiveness of SMIP34 in treating ECa. Treatment of established and primary patient-derived ECa cells with SMIP34 resulted in a significant reduction of cell viability, colony formation ability, and induction of apoptosis. RNA-seq analyses showed that SMIP34-regulated genes were negatively correlated with ribosome biogenesis and eukaryotic translation pathways. Mechanistic studies showed that the Rix complex, which is essential for ribosomal biogenesis, is disrupted upon SMIP34 binding to PELP1. Biochemical assays confirmed that SMIP34 reduced ribosomal biogenesis and new protein synthesis. Further, SMIP34 enhanced the efficacy of mTOR inhibitors in reducing viability of ECa cells. SMIP34 is also effective in reducing cell viability in ECa organoids in vitro and explants ex vivo. Importantly, SMIP34 treatment resulted in a significant reduction of the growth of ECa xenografts. Collectively, these findings underscore the potential of SMIP34 in treating ECa.

CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening.

BACKGROUND: The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown. METHODS: We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments. RESULT: The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC. CONCLUSION: CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.

IL-7 promotes CD19-directed CAR-T cells proliferation through miRNA-98-5p by targeting CDKN1A.

CAR-T targeting CD19 have achieved significant effects in the treatment of B-line leukemia and lymphoma. However, the treated patients frequently relapsed and could not achieve complete remission. Therefore, improving the proliferation and cytotoxicity of CAR-T cells, reducing exhaustion and enhancing infiltration capacity are still issues to be solved. The IL-7 has been shown to enhance the memory characteristics of CAR-T cells, but the specific mechanism has yet to be elaborated. miRNAs play an important role in T cell activity. However, whether miRNA is involved in the activation of CAR-T cells by IL-7 has not yet been reported. Our previous study had established the 3rd generation CAR-T cells. The present study further found that IL-7 significantly increased the proliferation of anti-CD19 CAR-T cells, the ratio of CD4 + CAR + cells and the S phase of cell cycle. In vivo study NAMALWA xenograft model showed that IL-7-stimulated CAR-T cells possessed stronger tumoricidal efficiency. Further we validated that IL-7 induced CAR-T cells had low expression of CDKN1A and high expression of miRNA-98-5p. Additionally, CDKN1A was associated with miRNA-98-5p. Our results, for the first time, suggested IL-7 could conspicuously enhance the proliferation of CAR-T cells through miRNA-98-5p targeting CDKN1A expression, which should be applied to CAR-T production.

Astragalus improves intestinal barrier function and immunity by acting on intestinal microbiota to treat T2DM: a research review.

Diabetes is a significant chronic endocrine/metabolism disorder that can result in a number of life-threatening consequences. According to research, the gut microbiota is strongly linked to the development of diabetes, making it a viable target for diabetes treatment. The intestinal microbiota affects intestinal barrier function, organism immunity, and thus glucose metabolism and lipid metabolism. According to research, a disruption in the intestinal microbiota causes a decrease in short-chain fatty acids (SCFAs), alters the metabolism of bile acids (BAs), branched-chain amino acids (BCAAs), lipopolysaccharide (LPS), and endotoxin secretion, resulting in insulin resistance, chronic inflammation, and the progression to type 2 diabetes mellitus (T2DM). Astragali Radix is a medicinal herb of the same genus as food that has been extensively researched for treating diabetes mellitus with promising results in recent years. Polysaccharides, saponins, flavonoids, and other components are important. Among them, Astragaloside has a role in protecting the cellular integrity of the pancreas and liver, can leading to alleviation of insulin resistance and reducing blood glucose and triglyceride (TC) levels; The primary impact of Astragalus polysaccharides (APS) on diabetes is a decrease in insulin resistance, encouragement of islet cell proliferation, and suppression of islet ß cell death; Astragali Radix flavonoids are known to enhance immunity, anti-inflammatory, regulate glucose metabolism and control the progression of diabetes. This study summarizes recent studies on Astragali Radix and its group formulations in the treatment of type 2 diabetes mellitus by modulating the intestinal microbiota.

Orbicularis muscle fixation downward for the correction of congenital epiblepharon in Chinese patients.

BACKGROUND: Congenital epiblepharon (CE) is a congenital eyelid deformity unique to young individuals of Asian descendants, and it might cause a sequence of other complications such as corneal damage and ocular foreign body sensation. Surgery is the most effective approach to treat this condition. Here, this study evaluated the effectiveness and safety of the orbicularis muscle fixation downward (OMFD) procedure for correcting CE. METHODS: This study enrolled 29 patients who were diagnosed with CE. These patients experienced significant ocular irritation leading to epiphora and corneal injury and, therefore, they underwent the OMFD procedure that was performed by the same surgeon. The cases were divided into 3 grades according to postoperative outcomes. RESULTS: The OMFD procedure was performed on 55 lower lids of the 29 patients. The average age of the patients was 9.6 years. The mean follow-up duration was 17 months. No perioperative complications were observed, and successful surgical outcomes were achieved in all 29 patients. No postoperative necrosis, infection, or corneal epithelial injury occurred. None of the patients exhibited significant scarring. Three patients showed residual 1-3 eyelashes touching the nasal corneal or bulbar conjunctiva at the inner canthus during the last postoperative examination. These patients did not undergo further surgery as there were no obvious irritation symptoms or corneal damage. CONCLUSIONS: The fixation of the pretarsal orbicularis muscle is a simple and effective modification of the Hotz procedure to correct CE. The key aspect of this procedure is the suturing of the pretarsal orbicularis muscle and the lower eyelid retractors.