Histone Deacetylase SIRT1 Negatively Regulates the Differentiation of Interleukin-9-Producing CD4(+) T Cells.

Distinct metabolic programs support the differentiation of CD4(+) T cells into separate functional subsets. In this study, we investigated metabolic mechanisms underlying the differentiation of IL-9-producing CD4(+) T cells (Th9) in allergic airway inflammation and cancerous tumors. We found that histone deacetylase SIRT1 negatively regulated Th9 cell differentiation. A deficiency of SIRT1 induced by either conditional deletion in mouse CD4(+) T cells or the use of small interfering RNA (siRNA) in mouse or human T cells increased IL-9 production, whereas ectopic SIRT1 expression inhibited it. Notably, SIRT1 inhibited Th9 cell differentiation that regulated anti-tumor immunity and allergic pulmonary inflammation. Glycolytic activation through the mTOR-hypoxia-inducible factor-1α (HIF1α) was required for the differentiation of Th9 cells that conferred protection against tumors and is involved in allergic airway inflammation. Our results define the essential features of SIRT1-mTOR-HIF1α signaling-coupled glycolytic pathway in inducing Th9 cell differentiation, with implications for metabolic reprogramming as an immunotherapeutic approach.

Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective.

Unprecedented therapeutic targeting of previously undruggable proteins has now been achieved by molecular-glue-mediated proximity-induced degradation. As a small GTPase, G1 to S phase transition 1 (GSPT1) interacts with eRF1, the translation termination factor, to facilitate the process of translation termination. Studied demonstrated that GSPT1 plays a vital role in the acute myeloid leukemia (AML) and MYC-driven lung cancer. Thus, molecular glue (MG) degraders targeting GSPT1 is a novel and promising approach for treating AML and MYC-driven cancers. In this Perspective, we briefly summarize the structural and functional aspects of GSPT1, highlighting the latest advances and challenges in MG degraders, as well as some representative patents. The structure-activity relationships, mechanism of action and pharmacokinetic features of MG degraders are emphasized to provide a comprehensive compendium on the rational design of GSPT1 MG degraders. We hope to provide an updated overview, and design guide for strategies targeting GSPT1 for the treatment of cancer.

Selective Oxidation of Alcohol to Valuable Aldehydes Using Water as a Promoter in a Photoelectrochemical Cell.

Artificial photoelectrochemistry (PEC) has emerged as a promising and efficient technology for the sustainable conversion of solar energy into chemicals. In this study, we present a refined PEC process that enables the highly selective and stable production of piperonal and other valuable aldehydes through the oxidation of the corresponding alcohols. By employing Fe2O3 or TiO2 as the photoanode material and 2,2,6,6-tetramethylpiperidinooxy (TEMPO) as a redox mediator in an H2O/acetonitrile solution, we achieve 100% selectivity and a >95% Faradaic efficiency for piperonal production from piperonyl alcohol (PA) oxidation. Remarkably, we reveal the enhancing effect on the PA oxidation reactivity of appropriate-amount water in the solvent as it plays a crucial role in inhibiting the photoelectron-hole recombination efficiency and facilitating charge transfer. Mechanistic analysis suggests that TEMPO-mediated PA oxidation involves the formation of •O2- radicals by the reduction of oxygen on the cathode, resulting in water as the sole byproduct. Furthermore, our PEC oxidation system exhibits applications on the 100%-selective production of various conjugated aldehydes, including 4-anisaldehyde, cuminaldehyde, and the vitamin B6 derivative. By implementing a TiO2//Fe2O3 dual-photoanode system, we achieve an enhanced piperonal production rate of 31.2 µmol h-1 cm-2 at 1.0 V vs Ag/Ag+ and demonstrate its stability over a 102 h cyclic test, ensuring near-quantitative yield. This research illuminates the potential of the PEC strategy as a generally applicable method for the efficient production of high-value aldehydes.

Examining the paradox: increased malaria risk in children under 5 in female-headed households in Nigeria.

BACKGROUND: Nigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria. METHODS: Data from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs. RESULTS: Among all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P < 0.001). U5 children in MHHs had a greater likelihood of sleeping under a bed net the night before the survey than U5 children in FHHs (35.3% vs. 30.0%, P < 0.05). The prevalence of fever in the previous two weeks among U5 children was similar in MHHs and FHHs (35.4% vs. 31.4%), and the testing rates for malaria among U5 children who experienced febrile episodes were higher in MHHs than FHHs (22.4% vs. 15.4%, P < 0.05). Although not statistically significant, FHHs exhibited a higher percentage of U5 children testing positive for malaria compared to MHHs (87.8% vs. 78.9%). On the other hand, FHHs had higher education levels, overall wealth index scores, and a larger presence in urban areas compared to MHHs (P < 0.001). Moreover, FHHs reported higher adherence to malaria prevention awareness (P < 0.001). CONCLUSION: In Nigeria, FHHs enjoy relatively better socioeconomic conditions and stronger awareness of malaria prevention compared to their male-headed counterparts. Contrary to expectations, FHHs are at an increased risk of malaria in children under 5 years old. This phenomenon is associated with entrenched gender inequality and the challenges women face in accessing critical assets. As women in FHHs bear the responsibility of income generation while caring for their children, it is crucial to prioritize interventions that address malaria management in FHHs to reduce both malaria incidence and mortality rates.

Sr2HgGe2OS6: A Hg-Based Oxychalcogenide Infrared Nonlinear Optical Material Exhibiting Favorable Balance between a Large Band Gap and Strong Second Harmonic Generation Response.

Currently, oxychalcogenides with mixed-anion groups that integrate the property advantages of oxides (wide optical band gap) and chalcogenides [strong second harmonic generation (SHG) response] through chemical substitution engineering have attracted widespread interest and are considered to be important candidates for infrared (IR) nonlinear optical (NLO) materials. Herein, the first Hg-based oxychalcogenide Sr2HgGe2OS6 with mixed anion [GeOS3] units has been successfully synthesized through a spontaneous crystallization method, which exhibits a favorable balance between the strong SHG response (0.7 × AgGaS2) and large optical band gap (2.9 eV). In addition, Sr2HgGe2OS6 shows high laser-induced damage threshold (LIDT, 2.1 × AgGaS2) as well as phase-matching (PM) performance. Theoretical calculations indicate that the Sr2HgGe2OS6 encompasses large birefringence of 0.128@2090 nm (3.3 × AgGaS2) and its SHG density mainly comes from [HgS4] tetrahedra and [GeOS3] units. This work not only demonstrates that Sr2HgGe2OS6 is a promising IR NLO material but also provides new ideas for the exploration of Hg-based oxychalcogenide IR NLO materials.

Transcriptomic landscape reveals germline potential of porcine skin-derived multipotent dermal fibroblast progenitors.

According to estimations, approximately about 15% of couples worldwide suffer from infertility, in which individuals with azoospermia or oocyte abnormalities cannot be treated with assisted reproductive technology. The skin-derived stem cells (SDSCs) differentiation into primordial germ cell-like cells (PGCLCs) is one of the major breakthroughs in the field of stem cells intervention for infertility treatment in recent years. However, the cellular origin of SDSCs and their dynamic changes in transcription profile during differentiation into PGCLCs in vitro remain largely undissected. Here, the results of single-cell RNA sequencing indicated that porcine SDSCs are mainly derived from multipotent dermal fibroblast progenitors (MDFPs), which are regulated by growth factors (EGF/bFGF). Importantly, porcine SDSCs exhibit pluripotency for differentiating into three germ layers and can effectively differentiate into PGCLCs through complex transcriptional regulation involving histone modification. Moreover, this study also highlights that porcine SDSC-derived PGCLCs specification exhibit conservation with the human primordial germ cells lineage and that its proliferation is mediated by the MAPK signaling pathway. Our findings provide substantial novel insights into the field of regenerative medicine in which stem cells differentiate into germ cells in vitro, as well as potential therapeutic effects in individuals with azoospermia and/or defective oocytes.

Domiciliary monitoring of exhaled nitric oxide in the management of asthma: a pilot study.

BACKGROUND: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. METHODS: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. RESULTS: In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). CONCLUSIONS: The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.

Review on the pharmacological effects and pharmacokinetics of scutellarein.

Scutellarein is a flavonoid from Scutellaria baicalensis  Georgi that has been shown to have a variety of pharmacological activities. This review aims to summarize the pharmacological and pharmacokinetic studies on scutellarein and provide useful information for relevant scholars. Pharmacological studies indicate that scutellarein possesses a diverse range of pharmacological properties, including but not limited to anti-inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, and cardiovascular protective effects. Further investigation reveals that the pharmacological effects of scutellarein are driven by multiple mechanisms. These mechanisms encompass the scavenging of free radicals, inhibition of the activation of inflammatory signaling pathways and expression of inflammatory mediators, inhibition of the activity of crucial viral proteins, suppression of gluconeogenesis, amelioration of insulin resistance, improvement of cerebral ischemia-reperfusion injury, induction of apoptosis in cancer cells, and prevention of myocardial hypertrophy, among others. In summary, these pharmacological studies suggest that scutellarein holds promise for the treatment of various diseases. It is imperative to conduct clinical studies to further elucidate the therapeutic effects of scutellarein. However, it is worth noting that studies on the pharmacokinetics reveal an inhibitory effect of scutellarein on uridine 5'-diphosphate glucuronide transferases and cytochrome P450 enzymes, potentially posing safety risks.

The association of cardiometabolic multimorbidity and fear of falling among older adults: Data from the national health and aging trends study.

OBJECTIVES: Cardiometabolic diseases (CMDs) have been individually associated with fall-related outcomes, but their combined effect on fear of falling (FOF) has not been investigated. This study aims to examine the association between cardiometabolic multimorbidity and FOF in older adults. METHODS: Data from the National Health and Aging Trends Study, 4,295 community-dwelling older adults ≥ 65 years were analyzed in this longitudinal study. CMDs were assessed at baseline, including heart disease, diabetes, stroke, and hypertension. FOF was evaluated by asking participants if they worried about falling in the past month. Data were analyzed using multi-adjusted logistic regression. RESULTS: Cardiometabolic multimorbidity was associated with a higher risk of FOF. The combination of heart disease and diabetes showed the highest risk of FOF (OR = 3.47, 95 % CI: 1.63-7.40). CONCLUSIONS: These findings underscore the need for targeted interventions to mitigate the combined impact of cardiometabolic multimorbidity on FOF in older adults.

Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold.

OBJECTIVES: To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response (ABR) in adults using CE-Chirp to analyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold. METHODS: Subjects (aged 20-77 with a total of 100 ears) who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold, and pure tone air conduction hearing threshold tests were conducted at 0.5, 1.0, 2.0 and 4.0 kHz, respectively, to obtain pure tone listening threshold. The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups. The correlation, differences and statistical differences between the two tests at each frequency were analyzed for all subjects. The linear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established, and the feasibility of the equation was tested. RESULTS: There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold difference between different hearing level groups and different age groups (P>0.05). There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance (P<0.05), and linear regression analysis showed a significant linear correlation between the two (P<0.05). CONCLUSIONS: The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects' pure tone hearing threshold under certain conditions, and can be used as an audiological test method for forensic hearing impairment assessment.

LncRNA HEM2ATM improves obesity-associated adipose tissues meta-inflammation and insulin resistance by interacting with heterogeneous nuclear ribonucleoprotein U.

Obesity is a complicated metabolic disease characterized by meta-inflammation in adipose tissues. In this study, we explored the roles of a new long non-coding RNA (lncRNA), HEM2ATM, which is highly expressed in adipose tissue M2 macrophages, in modulating obesity-associated meta-inflammation and insulin resistance. HEM2ATM expression decreased significantly in adipose tissue macrophages (ATMs) obtained from epididymal adipose tissues of high-fat diet (HFD)-induced obese mice. Overexpression of macrophage HEM2ATM improved meta-inflammation and insulin resistance in the adipose tissues of HFD-fed mice. Functionally, HEM2ATM negatively regulated the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in macrophages. Mechanistically, HEM2ATM bound to heterogeneous nuclear ribonucleoprotein U (hnRNP U), suppressed hnRNP U translocation from the nucleus to the cytoplasm, hindered the function of cytoplasmic hnRNP U on TNF-α and IL-6 mRNA stabilization, and decreased the secretion of TNF-α and IL-6. Collectively, HEM2ATM is a novel suppressor of obesity-associated meta-inflammation and insulin resistance.

MTA1 localizes to the mitotic spindle apparatus and interacts with TPR in spindle assembly checkpoint regulation.

We previously identified a cell cycle-dependent periodic subcellular distribution of cancer metastasis-associated antigen 1 (MTA1) and unraveled a novel role of MTA1 in inhibiting spindle damage-induced spindle assembly checkpoint (SAC) activation in cancer cells. However, the more detailed subcellular localization of MTA1 in mitotic cells and its copartner in SAC regulation in cancer cells are still poorly understood. Here, through immunofluorescent colocalization analysis of MTA1 and alpha-tubulin in mitotic cancer cells, we reveal that MTA1 is dynamically localized to the spindle apparatus throughout the entire mitotic process. We also demonstrated a reversible upregulation of MTA1 expression upon spindle damage-induced SAC activation, and time-lapse imaging assays indicated that MTA1 silencing delayed the mitotic metaphase-anaphase transition in cancer cells. Further investigation revealed that MTA1 interacts and colocalizes with Translocated Promoter Region (TPR) on spindle microtubules in mitotic cells, and this interaction is attenuated on SAC activation. TPR is well-implicated in SAC regulation via binding the MAD1-MAD2 complex, however, no interactions between MTA1 and MAD1 or MAD2 were detected in our coimmunoprecipitation (co-IP) assays, suggesting that the MTA1-TPR may represent a distinct SAC-associated complex separate from the previously reported TPR-MAD1/MAD2 complex. Our data provide new insights into the subcellular localization and molecular function of MTA1 in SAC regulation in cancer, and indicate that intervention of the MTA1-TPR interaction may be effective to modulate SAC and hence chromosomal instability (CIN) in tumorigenesis.

Advances in radiotherapy and immunity in hepatocellular carcinoma.

Primary liver cancer is one of the most common malignant tumours worldwide; it caused approximately 830,000 deaths in 2020. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for over 80% of all cases. Various methods, including surgery, chemotherapy, radiotherapy, and radiofrequency ablation, have been widely used in the treatment of HCC. With the advancement of technology, radiotherapy has become increasingly important in the comprehensive treatment of HCC. However, due to the insufficient sensitivity of tumour cells to radiation, there are still multiple limitation in clinical application of radiotherapy. In recent years, the role of immunotherapy in cancer has been increasingly revealed, and more researchers have turned their attention to the combined application of immunotherapy and radiotherapy in the hope of achieving better treatment outcomes. This article reviews the progress on radiation therapy in HCC and the current status of its combined application with immunotherapy, and discusses the prospects and value of radioimmunotherapy in HCC.

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy.

Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.

Synthesis, Crystal Structure, and Nonlinear-Optical Properties of a Diamond-Like Chalcogenide Cu2GeS3.

Metal sulfides with diamond-like (DL) structures generally exhibit excellent mid-IR nonlinear-optical (NLO) properties. Here, Cu2GeS3 (CGS) as a member of the DL chalcogenides was synthesized by a high-temperature solid-state method, and the optical properties were carefully studied experimentally and theoretically. The results revealed that CGS has a large second harmonic generation (0.8 × AgGaSe2) and a moderate birefringence of 0.067 at 1064 nm. In addition, the linear and NLO properties of the A2MS3 (A = Cu, Li; M = Ge, Si) series of compounds were evaluated and compared with the help of first-principles calculations.

Microbe community composition differences of hand skin on similar lifestyle volunteers: a small-scale study.

AIMS: Human skin is the first barrier against pathogens and environmental hazards and the highest contact frequency occurs with the hands. Environmental and personal metabolic factors may affect skin microbes. This study was conducted to clarify the diversity in the skin microbial community that was mainly due to individual skin metabolites rather than lifestyle and environmental factors. METHODS AND RESULTS: Skin microbiota samples were collected from 11 volunteers who met similar lifestyle inclusion criteria. The V3-V4 region of the 16S rRNA gene was amplified. After library construction and sequencing, we compared the composition and diversity of the hand skin microbiota in different sexes and BMI groups with bioinformation analysis. The whole sequence data were annotated as 42 phyla, 538 families, and 1215 genera. Four dominant phyla accounted for 97% of the total including Actinobacteriota (50.18%), Firmicutes (23.85%), Proteobacteria (21.64%) and Bacteroidota (2.05%). The genera that were detected in all subjects with high relative abundance were Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Enhydrobacter, Escherichia-Shigella, Asaia and Micrococcus. CONCLUSIONS: The diversity and richness of the microbiota of male hand skin in our study was higher than that of females. Interestingly, Cutibacterium, Staphylococcus, and Corynebacterium might serve as important skin microbiota to distinguish sexes.

Elite youth athletes' mental health and its relationship with the talent development environment: A variable- and person-centred approach.

The present research sought to examine the prevalence of elite youth athletes' mental health and its relationship with talent development environments (TDEs). A sample of 248 Chinese elite youth athletes completed a self-report survey measuring demographic variables, TDE factors, and mental health outcomes including generalised anxiety disorder (GAD), depression, and athlete burnout. The results revealed moderate levels of burnout, with 19% of the participants meeting the diagnostic cut-off of GAD, and similar numbers for depression. The multiple regression analysis revealed alignment of expectations was the only TDE factor to significantly predict GAD and depression. Holistic quality preparation was the only significant TDE predictor of burnout. The results of cluster analysis suggested a three-cluster solution: cluster 1-"slightly below average TDE", cluster 2-"high TDE", and cluster 3-"very low TDE". Among the three clusters, cluster 2 had the lowest levels of GAD, depression, and burnout. Cluster 3 reported a higher burnout level than cluster 1, and the two clusters showed no differences in other two mental health outcomes. These findings suggest a need to manage mental health symptoms of elite youth athletes, and the roles of TDE could be considered in the management of mental health.

Inhibitory Effects of 3-Methylcholanthrene Exposure on Porcine Oocyte Maturation.

3-methylcholanthrene (3-MC) is a highly toxic environmental pollutant that impairs animal health. 3-MC exposure can cause abnormal spermatogenesis and ovarian dysfunction. However, the effects of 3-MC exposure on oocyte maturation and embryo development remain unclear. This study revealed the toxic effects of 3-MC exposure on oocyte maturation and embryo development. 3-MC with different concentrations of 0, 25, 50, and 100 µM was applied for in vitro maturation of porcine oocytes. The results showed that 100 µM 3-MC significantly inhibited cumulus expansion and the first polar body extrusion. The rates of cleavage and blastocyst of embryos derived from 3-MC-exposed oocytes were significantly lower than those in the control group. Additionally, the rates of spindle abnormalities and chromosomal misalignments were higher than those in the control group. Furthermore, 3-MC exposure not only decreased the levels of mitochondria, cortical granules (CGs), and acetylated α-Tubulin, but also increased the levels of reactive oxygen species (ROS), DNA damage, and apoptosis. The expression of cumulus expansion and apoptosis-related genes was abnormal in 3-MC-exposed oocytes. In conclusion, 3-MC exposure disrupted the nuclear and cytoplasmic maturation of porcine oocytes through oxidative stress.

Vitamin D receptor inhibits EMT via regulation of the epithelial mitochondrial function in intestinal fibrosis.

We previously showed that the vitamin D receptor (VDR) plays a crucial role in acute inflammatory bowel disease and that intestinal fibrosis is a common complication of Crohn's disease (CD). Epithelial-mesenchymal transition (EMT) is an important hallmark of fibrogenesis through which epithelial cells lose their epithelial phenotype and transform into mesenchymal cells. It is known that the VDR plays an essential role in epithelial integrity and mitochondrial function, but its role in intestinal fibrosis remains unknown. Here, we investigated whether the VDR is involved in epithelial mitochondrial dysfunction that results in EMT in intestinal fibrosis. Using human CD samples, intestine-specific VDR-KO mice, and fibroblast cellular models, we showed that the expression of the VDR was significantly lower in intestinal stenotic areas than in nonstenotic areas in patients with chronic CD. Genetic deletion of the VDR in the intestinal epithelium exacerbated intestinal fibrosis in mice administered with dextran sulfate sodium or 2,4,6-trinitrobenzene sulfonic acid, two experimental colitis inducers. In addition, we found that vitamin D dietary intervention regulated intestinal fibrosis by modulating the intestinal expression of the VDR. Mechanistically, knocking down the VDR in both CCD-18Co cells and human primary colonic fibroblasts promoted fibroblast activation, whereas VDR overexpression or VDR agonist administration inhibited fibroblast activation. Further analysis illustrated that the VDR inhibited EMT in the HT29 cell model and that mitochondrial dysfunction mediated epithelial integrity and barrier function in VDR-deficient epithelial cells. Together, our data for the first time demonstrate that VDR activation alleviates intestinal fibrosis by inhibiting fibroblast activation and epithelial mitochondria-mediated EMT.

Ultrabroad (3.7-17†µm) tunable femtosecond optical parametric amplifier based on BaGa4Se7 crystal.

We demonstrate the first (to the best of our knowledge) tunable femtosecond (fs) mid-infrared (MIR) optical parametric amplifier (OPA) based on BaGa4Se7 (BGSe) crystal with an ultra-broadband spectral range. Benefiting from the broad transparency range, high nonlinearity, and relatively large bandgap of BGSe, the MIR OPA pumped at 1030 nm with a repetition of 50 kHz has an output spectrum that is tunable across an extremely wide spectral range spanning from 3.7 to 17 µm. The maximum output power of the MIR laser source is measured as 10 mW at a center wavelength of 16 µm, corresponding to a quantum conversion efficiency of 5%. Power scaling is straightforwardly achieved by using a stronger pump in BGSe with an available large aperture size. A pulse width of 290 fs centered at 16 µm is supported by the BGSe OPA. Our experimental result indicates that BGSe crystal could serve as a promising nonlinear crystal for fs MIR generation with an ultra-broadband tuning spectral range via parametric downconversion for applications such as MIR ultrafast spectroscopy.