Near-infrared detection based on the excitation of hot electrons in Au/Si microcone array.

Although the photoresponse cut-off wavelength of Si is about 1100 nm due to the Si bandgap energy, the internal photoemission effect (IPE) of the Au/Si junction in Schottky detector can extend the absorption wavelength, which makes it a promising candidate for the Si-based infrared detector. However, due to low light absorption, low photon-electron interaction, and poor electron injection efficiency, the near-infrared light detection efficiency of the Schottky detector is still insufficient. The synergistic effect of Si nano/microstructures with a strong light trapping effect and nanoscale Au films with surface plasmon enhanced absorption may provide an effective solution for improving the detection efficiency. In this paper, a large-area periodic Si microcone array covered by an Au film has successfully been fabricated by one-time dry etching based on the mature polystyrene microspheres lithography technique and vacuum thermal deposition, and its properties for hot electron-based near infrared photodetection are investigated. Optical measurements show that the 20 nm-thick Au covered Si microcone array exhibits a low reflectance and a strong absorption (about 85%) in wide wavelength range (900 - 2500 nm), and the detection responsivity can reach a value as high as 17.1 and 7.0 mA/W at 1200 and 1310 nm under the front illumination, and 35.9 mA/W at 1310 nm under the back illumination respectively. 3D-FDTD simulation results show that the enhanced local electric field in the Au layer distributes near the air/Au interface under the front illumination and close to the Au/Si interface under the back illumination. The back illumination favors the injection of photo-generated hot electrons in Au layer into Si, which can explain the higher responsivity under the back illumination. Our research is expected to promote the practical application of Schottky photodetectors to Si-compatible near infrared photodetectors. .

Tumor purity-related genes for predicting the prognosis and drug sensitivity of DLBCL patients.

Background: Diffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics. Methods: Datasets from the Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factors that influenced the prognosis. Drug-sensitive prediction was performed to evaluate the value of the model. Results: VCAN, CD3G, and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68 + macrophages and CD8 + T cells was associated with better prognosis. In addition, CD3G+T cells ratio was significantly correlated with CD68 + macrophages, CD4 + T cells, and CD8 +T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB, and CD3G work well in predicting the prognosis and drug sensitivity. Conclusions: VCAN, CD3G, and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients. Funding: This work is supported by the Shenzhen High-level Hospital Construction Fund and CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-062).

Protocol for building synthetic protocell membranes that sense redox using synthetic phospholipids and natural lipids.

Sensing is a critical function of artificial cells; however, this is challenging to realize using bottom-up approaches. Here, we present a protocol for building protocell membranes that sense cues important for redox biochemistry and signaling by combining synthetic phospholipids and natural lipids. We detail procedures for building giant unilamellar vesicles as protocell models that fluoresce in response to the biologically significant redox agents peroxynitrite, hydrogen peroxide, and hydrogen sulfide. For complete details on the use and execution of this protocol, please refer to (i) Gutierrez and Aggarwal et al.1 as well as (ii) Erguven and Wang et al.2.

Design and bio-evaluation of novel millepachine derivatives targeting tubulin colchicine binding site for treatment of osteosarcoma.

Microtubules are recognized as an appealing target for cancer treatment. We designed and synthesized of novel tubulin colchicine binding site inhibitors based on millepachine. Biological evaluation revealed compound 5h exhibited significant antiproliferative activity against osteosarcoma cell U2OS and MG-63. And compound 5h also remarkably inhibited tubulin polymerization. Further investigations indicated compound 5h not only arrest U2OS cells cycle at the G2/M phases, but also induced U2OS cells apoptosis in dose-dependent manners. Moreover, compound 5h was verified to inhibit cell migration and angiogenesis of HUVECs, induce mitochondrial membrane potential decreased and promoted the elevation of ROS levels. Furthermore, compound 5h exhibited remarkable effects on tumor growth in vivo, and the TGI rate was up to 84.94 % at a dose of 20 mg/kg without obvious toxicity. These results indicated that 5h may be an appealing tubulin inhibitor for treatment of osteosarcoma.

Integrated Bioinformatic Analysis Reveals the Oncogenic, Survival, and Prognostic Characteristics of TPX2 in Hepatocellular Carcinoma.

Targeting protein for Xenopus kinesin-like protein 2 (TPX2), a well-known mitotic protein, has been linked to carcinogenesis in several cancers. This study investigated the role of TPX2 in hepatocellular carcinoma (HCC) from various aspects using bioinformatic analyses. TPX2 expression and its prognostic value in pan-cancers were analyzed using SangerBox. TPX2 expression and its association with prognosis, immune infiltration, tumor mutations, and signaling pathways in HCC were analyzed using UALCAN, BoxKaplan-Meier Plotter, GEPIA, Human Protein Atlas, TIMER 2.0, and SangerBox. Genes co-expressed with TPX2 in HCC were analyzed using the HCCDB database, followed by functional enrichment using SangerBox. Clinical predictive models were established based on TPX2 and its co-expressed genes using the ACLBI database. TPX2 expression significantly increased in pan-cancers and was associated with survival in nearly half of the cancer types. High TPX2 expression has been linked to poor survival outcomes in patients with HCC. TPX2 expression was positively correlated with abundant infiltration of immune cells (including B cells, CD4 + /CD8 + T cells, macrophages, neutrophils, and dendritic cells), TP53 mutation, and carcinogenesis-related pathways, such as the PI3K/AKT/mTOR pathway, cellular response to hypoxia, and tumor proliferation signature. Nineteen genes were found to be co-expressed with TPX2 in HCC, and these genes showed close positive correlations and were mainly implicated in cell cycle-related functions. A prognostic model established using TPX2 and its expressed genes could stratify HCC patients into high- and low-risk groups, with a significantly shorter survival time in high-risk groups. The prognostic model performed well in predicting 1-, 3-, and 5-year survival of patients with HCC, with areas under the curve of 0.801, 0.725, and 0.711, respectively. TPX2 functions as an oncogene in HCC, and its high expression is detrimental to the survival of patients with HCC. Thus, TPX2 may be a prognostic biomarker and potential therapeutic target for HCC.

The cumulative antitumor effects of regorafenib and radiotherapy in hepatocellular carcinoma.

Regorafenib is a second-line standard treatment for hepatocellular carcinoma (HCC). However, the efficacy of regorafenib is often limited due to drug resistance, individual differences among patients, and irrational drug use. Radiotherapy (RT) is an important method of localized HCC treatment, and combining RT with other therapies may exert a synergetic antitumor effect. Platelet-derived growth factor receptor-like (PDGFRL) is a tumor suppressor in various solid tumors. However, the function of PDGFRL in HCC is still unknown. In this study, we explored whether regorafenib and RT exert a synergetic effect on the treatment of HCC. The antitumor effect and mechanisms of the combination of regorafenib and RT were verified in a xenograft mouse model in vivo and in HCC cells in vitro. The combination treatment significantly inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. PDGFRL, a potential target of regorafenib, was increased after cumulative treatment in HCC cells, and PDGFRL suppressed HCC cell proliferation and promoted apoptosis by inhibiting STAT3 pathway activation. Furthermore, the cumulative antitumor effect was dependent on the upregulated expression of PDGFRL and inhibition of STAT3 signaling pathway activation in HCC cells. This study increased the understanding of the molecular mechanism underlying the effect of regorafenib plus RT on HCC and provided a theoretical basis for the clinical practice of HCC.

Mesenchymal stromal cells ameliorate mitochondrial dysfunction in α cells and hyperglucagonemia in type 2 diabetes via SIRT1/FoxO3a signaling.

Dysregulation of α cells results in hyperglycemia and hyperglucagonemia in type 2 diabetes mellitus (T2DM). Mesenchymal stromal cell (MSC)-based therapy increases oxygen consumption of islets and enhances insulin secretion. However, the underlying mechanism for the protective role of MSCs in α-cell mitochondrial dysfunction remains unclear. Here, human umbilical cord MSCs (hucMSCs) were used to treat 2 kinds of T2DM mice and αTC1-6 cells to explore the role of hucMSCs in improving α-cell mitochondrial dysfunction and hyperglucagonemia. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay (ELISA). Mitochondrial function of α cells was assessed by the Seahorse Analyzer. To investigate the underlying mechanisms, Sirtuin 1 (SIRT1), Forkhead box O3a (FoxO3a), glucose transporter type1 (GLUT1), and glucokinase (GCK) were assessed by Western blotting analysis. In vivo, hucMSC infusion improved glucose and insulin tolerance, as well as hyperglycemia and hyperglucagonemia in T2DM mice. Meanwhile, hucMSC intervention rescued the islet structure and decreased α- to ß-cell ratio. Glucagon secretion from αTC1-6 cells was consistently inhibited by hucMSCs in vitro. Meanwhile, hucMSC treatment activated intracellular SIRT1/FoxO3a signaling, promoted glucose uptake and activation, alleviated mitochondrial dysfunction, and enhanced ATP production. However, transfection of SIRT1 small interfering RNA (siRNA) or the application of SIRT1 inhibitor EX-527 weakened the therapeutic effects of hucMSCs on mitochondrial function and glucagon secretion. Our observations indicate that hucMSCs mitigate mitochondrial dysfunction and glucagon hypersecretion of α cells in T2DM via SIRT1/FoxO3a signaling, which provides novel evidence demonstrating the potential for hucMSCs in treating T2DM.

Benzylic Trifluoromethyl Accelerates 1,6-Elimination Toward Rapid Probe Activation.

Activity-based detection of hydrogen sulfide in live cells can expand our understanding of its reactivity and complex physiological effects. We have discovered a highly efficient method for fluorescent probe activation, which is driven by H2S-triggered 1,6-elimination of an α-CF3-benzyl to release resorufin. In detecting intracellular H2S, 4-azido-(α-CF3)-benzyl resorufin offers significantly faster signal generation and improved sensitivity compared to 4-azidobenzyl resorufin. Computed free energy profiles for the 1,6-elimination process support the hypothesis that a benzylic CF3 group can reduce the activation energy barrier toward probe activation. This novel probe design allows for near-real-time detection of H2S in HeLa cells under stimulation conditions.

Analysis of the clinical characteristics and risk factors associated with contralateral hip fracture after initial hip fracture in elderly patients: a retrospective cohort study.

Fractures of the contralateral hip may easily occur in elderly patients after an initial hip fracture. The aim of this study was to investigate the clinical characteristics and major predisposing risk factors of contralateral hip fracture after initial hip fracture in the elderly, to provide a clinical basis for preventing contralateral hip fracture. The data of 1586 patients who had sustained first or second hip fractures and had been surgically treated in our department were retrospectively analyzed. Potential predictive factors for contralateral hip fracture and descriptive statistics associated with surgery (such as blood loss, operation time, and length of hospital stay) were recorded. Of these patients, 133 (8.4%) suffered contralateral hip fracture. The rates of contralateral fracture after femoral neck and intertrochanteric fracture were 5.4% and 10.7% respectively (P < 0.01). Fifty-four cases of contralateral hip fracture occurred within one year, an incidence of 40.6%, while 95 cases (71.4%) and 105 cases (78.9%) occurred within two and three years, respectively, with a interval duration of 21.6 months. The risk factors for contralateral hip fracture were found to be age, type of first fracture, bone mineral density, the Singh index, and concomitant internal medical diseases, which were found to be significantly associated with an increased risk of contralateral hip fracture in multivariate logistic regression analysis (P < 0.05). In conclusion, the presence of concomitant internal diseases, type of first fracture, bone mineral density, the Singh index, and age were found to be significant predictors of the risk of contralateral hip fracture in elderly patients after a first hip fracture.

A Novel Data Fusion Strategy of GC-MS and 1H NMR Spectra for the Identification of Different Vintages of Maotai-flavor Baijiu.

Counterfeit Baijiu has been emerging because of the price variances of real-aged Chinese Baijiu. Accurate identification of different vintages is of great interest. In this study, the combination of gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy was applied for the comprehensive analysis of chemical constituents for Maotai-flavor Baijiu. Furthermore, a novel data fusion strategy combined with machine learning algorithms has been established. The results showed that the midlevel data fusion combined with the random forest algorithm were the best and successfully applied for classification of different Baijiu vintages. A total of 14 differential compounds (belonging to fatty acid ethyl esters, alcohols, organic acids, and aldehydes) were identified, and used for evaluation of commercial Maotai-flavor Baijiu. Our results indicated that both volatiles and nonvolatiles contributed to the vintage differences. This study demonstrated that GC-MS and 1H NMR spectra combined with a data fusion strategy are practical for the classification of different vintages of Maotai-flavor Baijiu.

Activation of the Wnt/ß-catenin signalling pathway enhances exosome production by hucMSCs and improves their capability to promote diabetic wound healing.

BACKGROUND: The use of stem cell-derived exosomes (Exos) as therapeutic vehicles is receiving increasing attention. Exosome administration has several advantages over cell transplantation, thus making exosomes promising candidates for large-scale clinical implementation and commercialization. However, exosome extraction and purification efficiencies are relatively low, and therapeutic heterogeneity is high due to differences in culture conditions and cell viability. Therefore, in this study, we investigated a priming procedure to enhance the production and therapeutic effects of exosomes from human umbilical cord mesenchymal stem cells (hucMSCs). After preconditioning hucMSCs with agonists/inhibitors that target the Wnt/ß-catenin pathway, we assessed both the production of exosomes and the therapeutic efficacy of the optimized exosomes in the context of diabetic wound healing, hoping to provide a safer, more stable and more effective option for clinical application. RESULTS: The Wnt signalling pathway agonist CHIR99021 increased exosome production by 1.5-fold without causing obvious changes in the characteristics of the hucMSCs or the size of the exosome particles. Further studies showed that CHIR99021 promoted the production of exosomes by facilitating exocytosis. This process was partly mediated by SNAP25. To further explore whether CHIR99021 changed the cargo that was loaded into the exosomes and its therapeutic effects, we performed proteomic and transcriptomic analyses of exosomes from primed and control hucMSCs. The results showed that CHIR99021 significantly upregulated the expression of proteins that are associated with cell migration and wound healing. Animal experiments confirmed that, compared to control hucMSC-derived exosomes, CHIR99021-pretreated hucMSC-derived exosomes (CHIR-Exos) significantly accelerated wound healing in diabetic mice, enhanced local collagen deposition, promoted angiogenesis, and reduced chronic inflammation. Subsequent in vitro experiments confirmed that the CHIR-Exos promoted wound healing by facilitating cell migration, inhibiting oxidative stress-induced apoptosis, and preventing cell cycle arrest. CONCLUSIONS: The Wnt agonist CHIR99021 significantly increased exosome secretion by hucMSCs, which was partly mediated by SNAP25. Notably, CHIR99021 treatment also significantly increased the exosomal levels of proteins that are associated with wound healing and cell migration, resulting in enhanced acceleration of wound healing. All of these results suggested that pretreatment of hucMSCs with CHIR99021 not only promoted exosome production but also improved the exosome therapeutic efficacy, thus providing a promising option for large-scale clinical implementation and commercialization.

Ocular biometric characteristics of Han ethnicity in Tianjin and Uyghur ethnicity in Xinjiang undergoing cataract surgery.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.

A Comprehensive Study of NF3-Based Selective Etching Processes: Application to the Fabrication of Vertically Stacked Horizontal Gate-All-around Si Nanosheet Transistors.

In this paper, we demonstrate a comprehensive study of NF3-based selective etching processes for inner spacer formation and for channel release, enabling stacked horizontal gate-all-around Si nanosheet transistor architectures. A cyclic etching process consisting of an oxidation treatment step and an etching step is proposed and used for SiGe selective etching. The cyclic etching process exhibits a slower etching rate and higher etching selectivity compared to the direct etching process. The cycle etching process consisting of Recipe 1, which has a SiGe etching rate of 0.98 nm/cycle, is used for the cavity etch. The process achieved good interlayer uniformity of cavity depth (cavity depth ≤ 5 ± 0.3 nm), while also obtaining a near-ideal rectangular SiGe etch front shape (inner spacer shape = 0.84) and little Si loss (0.44 nm@ each side). The cycle etching process consisting of Recipe 4 with extremely high etching selectivity is used for channel release. The process realizes the channel release of nanosheets with a multi-width from 30 nm to 80 nm with little Si loss. In addition, a selective isotropic etching process using NF3/O2/Ar gas mixture is used to etch back the SiN film. The impact of the O2/NF3 ratio on the etching selectivity of SiN to Si and the surface roughness of SiN after etching is investigated. With the introduction of O2 into NF3/Ar discharge, the selectivity increases sharply, but when the ratio of O2/NF3 is up to 1.0, the selectivity tends to a constant value and the surface roughness of SiN increases rapidly. The optimal parameter is O2/NF3 = 0.5, resulting in a selectivity of 5.4 and a roughness of 0.19 nm.

Optimizing the Effects of a Comprehensive Emergency Nursing Model on Rescued Patients with Acute Myocardial Infarction in the Cardiology Department.

Background: Acute myocardial infarction (AMI) requires timely and efficient intervention to mitigate adverse events and enhance patient prognosis. However, variations in emergency nursing protocols may impact treatment outcomes. Therefore, assessing the effectiveness of a comprehensive emergency nursing model, encompassing advanced assessment techniques and tailored interventions, is important for refining care strategies. Objective: This study aimed to assess the optimization effect of a comprehensive emergency nursing model on rescued patients diagnosed with acute myocardial infarction (AMI) within the cardiology department. Methods: This retrospective study analyzed data from 80 cases of AMI patients admitted to our hospital between January and June 2023. The study was conducted within our hospital's cardiology department. The participants were divided into two groups: an intervention group (n=40) and a control group (n=40). The intervention group received care under the comprehensive, optimized emergency nursing model, while the control group received standard emergency care. Evaluation parameters comprised rescue time, effectiveness of emergency treatment, and nursing satisfaction. Results: No significant differences in baseline patient characteristics were observed between the two groups. However, the intervention group demonstrated notable reductions in triage assessment time, completion of electrocardiograms, venous blood sampling, administration of intravenous medication, and overall emergency duration compared to the control group (P < .001). Additionally, the clinical complication rate in the intervention group, particularly incidences of heart failure and myocardial infarction recurrence, was significantly lower than that in the control group (P < .05). Patients in the intervention group reported significantly higher nursing satisfaction scores compared to their counterparts in the control group (P < .001). Conclusion: The comprehensive emergency nursing model substantially decreased rescue time for AMI patients, minimized complication rates, and enhanced patient satisfaction with nursing care. This model presents an efficacious strategy for optimizing the rescue process of acute myocardial infarction patients within the cardiology department.

Heterotrimeric Gα-subunit regulates flower and fruit development in CLAVATA signaling pathway in cucumber.

Flowers and fruits are the reproductive organs in plants and play essential roles in natural beauty and the human diet. CLAVATA (CLV) signaling has been well characterized as regulating floral organ development by modulating shoot apical meristem (SAM) size; however, the signaling molecules downstream of the CLV pathway remain largely unknown in crops. Here, we found that functional disruption of CsCLV3 peptide and its receptor CsCLV1 both resulted in flowers with extra organs and stumpy fruits in cucumber. A heterotrimeric G protein α-subunit (CsGPA1) was shown to interact with CsCLV1. Csgpa1 mutant plants derived from gene editing displayed significantly increased floral organ numbers and shorter and wider fruits, a phenotype resembling that of Csclv mutants in cucumber. Moreover, the SAM size was enlarged and the longitudinal cell size of fruit was decreased in Csgpa1 mutants. The expression of the classical stem cell regulator WUSCHEL (WUS) was elevated in the SAM, while the expression of the fruit length stimulator CRABS CLAW (CRC) was reduced in the fruit of Csgpa1 mutants. Therefore, the Gα-subunit CsGPA1 protein interacts with CsCLV1 to inhibit floral organ numbers but promote fruit elongation, via repressing CsWUS expression and activating CsCRC transcription in cucumber. Our findings identified a new player in the CLV signaling pathway during flower and fruit development in dicots, increasing the number of target genes for precise manipulation of fruit shape during crop breeding.

Temperature-sensitive metal-enhanced fluorescence and plasmon resonance energy transfer.

Experimental decoupling of the effects of plasmon resonance energy transfer (PRET) and metal-enhanced fluorescence (MEF) within the same nanometal-fluorophore pair is fascinating but challenging. In this study, we presented a possible solution for this by coating plasmonic Au nanoparticles (AuNPs) with temperature-sensitive poly(N-isopropylacrylamide) (pNIPAM) shells and R6G hybrids, termed the Au@p-R nanoplatform, which could reversibly adjust the separation between dyes and the AuNP surface, enabling an ON/OFF switch between MEF and PRET. In our optimization process, we discovered that 20 kDa of pNIPAM causes an MEF effect owing to an appropriate shrinking distance of 6.86 ± 0.85 nm. This dual-model nanoplatform exhibits great potential for tracking temperature-dependent transitions.

Clinical and functional characterization of a novel KCNJ11 (c.101G > A, p.R34H) mutation associated with maturity-onset diabetes mellitus of the young type 13.

PURPOSE: This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets. METHODS: Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS). RESULTS: Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25. CONCLUSION: For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic ß-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation.

Biomimetic Vesicles with Designer Phospholipids Can Sense Environmental Redox Cues.

Cell-like materials that sense environmental cues can serve as next-generation biosensors and help advance the understanding of intercellular communication. Currently, bottom-up engineering of protocell models from molecular building blocks remains a grand challenge chemists face. Herein, we describe giant unilamellar vesicles (GUVs) with biomimetic lipid membranes capable of sensing environmental redox cues. The GUVs employ activity-based sensing through designer phospholipids that are fluorescently activated in response to specific reductive (hydrogen sulfide) or oxidative (hydrogen peroxide) conditions. These synthetic phospholipids are derived from 1,2-dipalmitoyl-rac-glycero-3-phosphocholine and they possess a headgroup with heterocyclic aromatic motifs. Despite their structural deviation from the phosphocholine headgroup, the designer phospholipids (0.5-1.0 mol %) mixed with natural lipids can vesiculate, and the resulting GUVs (7-20 µm in diameter) remain intact over the course of redox sensing. All-atom molecular dynamics simulations gave insight into how these lipids are positioned within the hydrophobic core of the membrane bilayer and at the membrane-water interface. This work provides a purely chemical method to investigate potential redox signaling and opens up new design opportunities for soft materials that mimic protocells.

The novel probiotic preparation based on Lactobacillus spp. mixture on the intestinal bacterial community structure of Cherry Valley duck.

The development and utilization of probiotics have many environmental benefits when they are used to replace antibiotics in animal production. In this study, intestinal lactic acid bacteria were isolated from the intestines of Cherry Valley ducks. Probiotic lactic acid bacterial strains were screened for antibacterial activity and tolerance to produce a Lactobacillus spp. mixture. The effects of the compound on the growth performance and intestinal flora of Cherry Valley ducks were studied. Based on the results of the antibacterial activity and tolerance tests, the highly active strains Lactobacillus casei 1.2435, L. salivarius L621, and L. salivarius L4 from the intestines of Cherry Valley ducks were selected. The optimum ratio of L. casei 1.2435, L. salivarius L621, and L. salivarius L4 was 1:1:2, the amount of inoculum used was 1%, and the fermentation time was 14 h. In vivo experiments showed that compared with the control group, the relative abundances of intestinal Lactobacillus and Blautia were significantly increased in the experimental group fed the lactobacilli compound (P < 0.05); the relative abundances of Parabacteroides, [Ruminococcus]_torques_group, and Enterococcus were significantly reduced (P < 0.05), and the growth and development of the dominant intestinal flora were promoted in the Cherry Valley ducks. This study will provide more opportunities for Cherry Valley ducks to choose microecological agents for green and healthy breeding.

Microecological regulation in HCC therapy: Gut microbiome enhances ICI treatment.

The exploration of the complex mechanisms of cancer immunotherapy is rapidly evolving worldwide, and our focus is on the interaction of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs), particularly as it relates to the regulatory role of the gut microbiome. An important basis for the induction of immune responses in HCC is the presence of specific anti-tumor cells that can be activated and reinforced by ICIs, which is why the application of ICIs results in sustained tumor response rates in the majority of HCC patients. However, mechanisms of acquired resistance to immunotherapy in unresectable HCC result in no long-term benefit for some patients. The significant heterogeneity of inter-individual differences in the gut microbiome in response to treatment with ICIs makes it possible to target modulation of specific gut microbes to assist in augmenting checkpoint blockade therapies in HCC. This review focuses on the complex relationship between the gut microbiome, host immunity, and HCC, and emphasizes that manipulating the gut microbiome to improve response rates to cancer ICI therapy is a clinical strategy with unlimited potential.