Application of uniportal video-assisted thoracoscopic surgery for segmentectomy in early-stage non-small cell lung cancer: A narrative review.

Uniportal video-assisted thoracoscopic surgery (UVATS) segmentectomy has emerged as an effective approach for managing early-stage non-small-cell lung cancer (NSCLC). Compared to conventional open and thoracoscopic surgeries, this minimally invasive surgical technique offers multiple benefits, including reduced postoperative discomfort, shorter hospital stays, expedited recovery, fewer complications, and superior cosmetic outcomes. Particularly advantageous in preserving lung function, UVATS segmentectomy is a compelling option for patients with compromised lung capabilities or limited pulmonary reserve. Notably, it demonstrates promising oncological results in early-stage NSCLC, with long-term survival rates comparable to those of lobectomies. Skilled thoracic surgeons can ensure a safe and effective execution of UVATS despite the potential technical challenges posed by complex tumor locations that may hinder visibility and maneuverability within the thoracic cavity. This study provided a comprehensive review of the literature and existing studies on UVATS segmentectomies. It delves into the evolution of the technique, its current applications, and the balance between its benefits and limitations. This discussion extends the technical considerations, challenges, and prospects of UVATS segmentectomy. Furthermore, it aimed to update advancements in segmentectomy for treating early-stage NSCLC, offering in-depth insights to thoracic surgeons to inform more scientifically grounded and patient-specific surgical decisions.

Characteristics of inclusions in chang 7 member and shale oil accumulation stages in Zhijing-Ansai area, Ordos Basin.

In order to further clarify the shale oil accumulation period of the Chang 7 member of the Mesozoic Triassic Yanchang Formation in the Zhijing-Ansai area of the central Ordos Basin, Using fluid inclusion petrography analysis, microscopic temperature measurement, salinity analysis and fluorescence spectrum analysis methods, combined with the burial history-thermal history recovery in the area, the oil and gas accumulation period of the Chang 7 member of the Yanchang Formation in the Zhijing-Ansai area was comprehensively analyzed. Sixteen shale oil reservoir samples of the Mesozoic Triassic Yanchang Formation in seven typical wells in the study area were selected.The results show that the fluid inclusions in the Chang 7 member of Yanchang Formation can be divided into two stages. The first stage inclusions mainly develop liquid hydrocarbon inclusions and a large number of associated brine inclusions, which are mainly beaded in fracture-filled quartz and fracture-filled calcite. The fluorescence color is blue and blue-green, and the homogenization temperature of the associated brine inclusions is between 90-110°C. The second stage inclusions are mainly gas-liquid two-phase hydrocarbon inclusions, gas inclusions and asphalt inclusions. Most of them are distributed in the fracture-filled quartz, and the temperature of the associated brine inclusions is between 120-130°C. Fluid inclusions in Chang 7 member of the Yanchang Formation can be divided into two stages. The CO2 inclusions and high temperature inclusions in the Chang 7 member of the Yanchang Formation are mainly derived from deep volcanic activity in the crust.

Linc00511 Promotes Thyroid Cancer Through the miR-4739/RNF38 Pathway.

Objective: To analyze the effect of Linc00511 on thyroid cancer through the miR-4739/RNF38 pathway. Methods: A total of 78 patients in our hospital from July 2020 to July 2021 were collected, which were diagnosed with thyroid cancer after clinicopathological examination. Their cancer tissue samples were included in the thyroid cancer tissue group, and the fat 2 cm tissue samples were included in the para-cancer tissue group. Real-time quantitative PCR was used to detect the expression of Linc00511, miR-4739 and RNF38 in tissue samples from the two groups. Statistical analysis of data was performed using SPSS26.0. The correlation between Linc00511, miR-4739 and RNF38 were analyzed by Pearson's correlation coefficient. The expression of Linc00511 in thyroid cancer tissues with different clinicopathological characteristics were compared. Results: The expression levels of Linc00511 and RNF38 in thyroid cancer group were significantly higher than paracancer group, while miR-4739 levels were significantly lower (P < .05). Pearson correlation coefficient analysis showed that there was significant negative correlation between Linc00511 and miR-4739 expression and significant positive correlation between Linc00511 and RNF38 expression (P < .05). There was no significant difference in the expression of Linc00511 among different ages, sexes, and cancer types (P > .05). The expression of Linc00511 in patients with TNM stages I, II, and III were increased with the increase of TNM stage (P < .05). The expression of Linc00511 in patients with tumor diameter ≥1 cm was higher than that in patients with tumor diameter <1 cm and the difference was statistically significant (P < .05). Conclusion: Linc00511 and RNF38 were significantly overexpressed in thyroid cancer tissues, while miR-4739 was significantly underexpressed. In thyroid cancer, Linc00511 can promote the invasion and metastasis of thyroid cancer cells by targeting miR-4739 and RNF38, and its expression level may reflect the progression of thyroid cancer, which can provide target reference for the clinical treatment of thyroid cancer.

Tracheobronchopathia osteochondroplastica concurrent with peripheral lung cancer: a case report and perioperative considerations.

Background: Tracheobronchopathia osteochondroplastica (TPO) is a rare, benign, chronic disorder of unknown etiology. It is characterized by submucosal nodules, often calcified, which predominantly affect the anterolateral aspects of the trachea and main bronchi, while sparing the posterior bronchial wall. The co-occurrence of TPO and lung cancer is exceedingly rare. This report presents a case of TPO association with early-stage lung cancer, which was managed through surgical intervention. No active treatment was undertaken for the TPO. Case Description: A patient presented with a nodule in the right upper lobe, which was identified during a computed tomography (CT) scan of the chest, suggestive of early-stage lung cancer. Concurrently, multiple calcifications in the cartilaginous rings of the trachea were noted. Bronchoscopy revealed distinctive "pebblestone" nodules along the anterior and lateral tracheal walls, indicative of extensive TPO. The patient underwent bronchofiberscopy, which showed patency in the bronchial lumen of the right lung's upper lobe. A biopsy was not undertaken during this procedure. Comprehensive preoperative tests, including a blood biochemical examination, tumor-marker tests, lung-function tests, head-enhanced magnetic resonance imaging, abdominal ultrasound, and whole-body bone emission CT revealed no significant abnormalities. Despite this, the patient declined a whole-body positron emission tomography (PET)-CT scan. Given the potential malignancy of nodules in the right lung's upper lobe, the lobectomy for lung cancer was carried out, a procedure that would have proceeded irrespective of the presence or absence of TPO. Preoperative planning for potential tracheal intubation difficulties involved consultation with the anesthesiologist, resulting in a smooth intraoperative process. The pathology confirmed invasive adenocarcinoma. Post-surgery, the patient developed an infection in the right lung's lower lobe, identified as pseudomonas aeruginosa and Klebsiella pneumoniae through sputum culture and bronchoscopic lavage. Treatment with meropenem for 2 weeks, as guided by drug sensitivity results and respiratory advice, led to an improvement, allowing for discharge. A follow-up lung CT four months post-operation showed inflammation absorption in the right lower lobe. Conclusions: Surgical resection in cases of TPO association with lung cancer may have an increased risk of postoperative pulmonary infection. Proactive intraoperative sputum aspiration by anesthesiologists and the postoperative reinforcement of anti-infection measures, guided by drug sensitivity results, are recommended.

Liproxstatin-1 attenuates acute hypertriglyceridemic pancreatitis through inhibiting ferroptosis in rats.

Ferroptosis is closely associated with inflammatory diseases, including acute pancreatitis (AP); however, the involvement of ferroptosis in hypertriglyceridemic pancreatitis (HTGP) remains unclear. In the present study, we aimed to explore the relationship between lipid metabolism and ferroptosis in HTGP and the alleviating effect of liproxstatin-1 (Lip-1) in vivo. This study represents the first exploration of lipid metabolism and endoplasmic reticulum stress (ERS) in HTGP, targeting ferroptosis as a key factor in HTGP. Hypertriglyceridemia (HTG) was induced under high-fat diet conditions. Cerulein was then injected to establish AP and HTGP models. Lip-1, a specific ferroptosis inhibitor, was administered before the induction of AP and HTGP in rats, respectively. Serum triglyceride, amylase, inflammatory factors, pathological and ultrastructural structures, lipid peroxidation, and iron overload indicators related to ferroptosis were tested. Moreover, the interaction between ferroptosis and ERS was assessed. We found HTG can exacerbate the development of AP, with an increased inflammatory response and intensified ferroptosis process. Lip-1 treatment can attenuate pancreatic injury by inhibiting ferroptosis through lipid metabolism and further resisting activations of ERS-related proteins. Totally, our results proved lipid metabolism can promote ferroptosis in HTGP by regulating ACSL4/LPCAT3 protein levels. Additionally, ERS may participate in ferroptosis via the Bip/p-EIF2α/CHOP pathway, followed by the alleviating effect of Lip-1 in the rat model.

Chaiqin Chengqi Decoction as an adjuvant treatment for mild/moderately severe hypertriglyceridemic acute pancreatitis: A retrospective study.

BACKGROUND: Hypertriglyceridemia is the third leading cause of acute pancreatitis (AP), and its incidence is increasing. Due to its relatively insidious etiology, it is easy to be ignored in the early stages. In China, Chaiqin Chengqi Decoction (CQCQD) has long been employed for treating AP. AIM: To evaluate the effectiveness of CQCQD in patients diagnosed with mild/ moderately severe hypertriglyceridemic AP (HTG-AP). METHODS: In this study, the clinical data of 39 patients with HTG-AP admitted from January 2019 to November 2022 were collected. The changes of blood lipids, gastrointestinal symptoms, and abdominal pain before and after treatment were analyzed and compared between the two groups. RESULTS: Twenty patients were treated with the conventional HTG-AP regimen, and 19 patients were additionally treated with CQCQD. After receiving treatment, the triglycerides (TG) level of the CQCQD group was lower than that of the CQCQD group (3.14 ± 0.25 mmol/L vs 4.96 ± 0.47 mmol/L, P < 0.01). After 3 d of treatment, the patients in the CQCQD group had more bowel movements than the control group (2.51 ± 0.25 times vs 1.00 ± 0.17 times, P = 0.01). The gastrointestinal function of most patients returned to normal, and the acute gastrointestinal injury score was significantly lower than that of the control group (0.11 ± 0.07 vs 0.42 ± 0.11, P < 0.01). CONCLUSION: In patients with HTG-AP, CQCQD can significantly reduce the TG level, shorten the recovery time of defecation, significantly improve the gastrointestinal function.

Temperature-Induced Interface Hybridization of WC Boosts NiCu Activity for Alkaline Hydrogen Oxidation Reaction.

The development of non-precious hydrogen oxidation reaction (HOR) catalysts is a major challenge for the commercialization of Pt-free fuel cells. Herein, a temperature-induced phase hybridization method is reported that greatly improves the catalytic performance of NiCu alloy for the HOR. The migration of W atoms hybridizes the interface of tungsten oxide (WOx) and tungsten carbide (WC) at the onset reduction temperature of WOx, leading to a greatly weakened H binding energy and an optimized OH binding energy, which endows NiCuW/WOx-WC@WC with favorable stability and CO resistance during HOR. The hybridization catalysts deliver a high mass activity of 29.37 mA mg-1 Ni and reach a peak power of 298 mW.cm-2 in H2-O2 anion exchange membrane fuel cells (AEMFCs).

Deep-Reinforcement-Learning-Based Joint Energy Replenishment and Data Collection Scheme for WRSN.

With the emergence of wireless rechargeable sensor networks (WRSNs), the possibility of wirelessly recharging nodes using mobile charging vehicles (MCVs) has become a reality. However, existing approaches overlook the effective integration of node energy replenishment and mobile data collection processes. In this paper, we propose a joint energy replenishment and data collection scheme (D-JERDG) for WRSNs based on deep reinforcement learning. By capitalizing on the high mobility of unmanned aerial vehicles (UAVs), D-JERDG enables continuous visits to the cluster head nodes in each cluster, facilitating data collection and range-based charging. First, D-JERDG utilizes the K-means algorithm to partition the network into multiple clusters, and a cluster head selection algorithm is proposed based on an improved dynamic routing protocol, which elects cluster head nodes based on the remaining energy and geographical location of the cluster member nodes. Afterward, the simulated annealing (SA) algorithm determines the shortest flight path. Subsequently, the DRL model multiobjective deep deterministic policy gradient (MODDPG) is employed to control and optimize the UAV instantaneous heading and speed, effectively planning UAV hover points. By redesigning the reward function, joint optimization of multiple objectives such as node death rate, UAV throughput, and average flight energy consumption is achieved. Extensive simulation results show that the proposed D-JERDG achieves joint optimization of multiple objectives and exhibits significant advantages over the baseline in terms of throughput, time utilization, and charging cost, among other indicators.

Characterization of three novel stem rot pathogens and their antagonistic endophytic bacteria associated with Cistanche deserticola.

Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola.

ZEB2 alleviates Hirschsprung's-associated enterocolitis by promoting the proliferation and differentiation of enteric neural precursor cells via the Notch-1/Jagged-2 pathway.

BACKGROUND: Hirschsprung's-associated enterocolitis (HAEC) is a prevalent complication of Hirschsprung's disease (HSCR). Zinc finger E-box binding homeobox 2 (ZEB2) and Notch-1/Jagged-2 are dysregulated in HSCR, but their role in HAEC progression remains poorly understood. We aimed to explore the role and underlying mechanism of enteric neural precursor cells (ENPCs) and the ZEB2/Notch-1/Jagged-2 pathway in HAEC development. METHODS: Colon tissues were collected from HSCR and HAEC patients. ENPCs were isolated from the HAEC group and stimulated by lipopolysaccharide (LPS). The expressions of ZEB2/Notch-1/Jagged-2 were measured using RT-qPCR and Western blot. Immunofluorescence and cell counting kit-8 assays were performed to assess the differentiation and proliferation of ENPCs. Inflammatory factors were measured by ELISA kits. Co-immunoprecipitation and bioinformatic analysis were used to explore the interaction between ZEB2 and Notch-1. Small interfering RNA and overexpression vectors were used to investigate the role and mechanism of ZEB2 and Notch-1 in regulating ENPCs' proliferation and differentiation during HAEC progression. RESULTS: We observed increased LPS in the colon tissues of HAEC, with downregulated ZEB2 expression and upregulated Notch-1/Jagged-2 expression. ZEB2 interacts with Notch-1. LPS treatment downregulated ZEB2 expression, upregulated Notch-1/Jagged-2 expression, and induced proliferation and differentiation disorders in ENPCs, which were reversed by the knockdown of Notch-1. Furthermore, overexpression of ZEB2 inhibited Notch-1/Jagged-2 signaling and ameliorated inflammation and dysfunction in LPS-induced ENPCs. Notch-1 overexpression enhanced LPS-induced dysfunction, but this effect was antagonized by the overexpression of ZEB2. CONCLUSION: Overexpression of ZEB2 ameliorates LPS-induced ENPCs' dysfunction via the Notch-1/Jagged-2 pathway, thus playing a role in HAEC.

Development of a risk-predicting score for hip preservation with bone grafting therapy for osteonecrosis.

Identification and differentiation of appropriate indications on hip preserving with bone grafting therapy remains a crucial challenge in the treatment of osteonecrosis of the femoral head (ONFH). A prospective cohort study on bone grafting therapy for ONFH aimed to evaluate hip survival rates, and to establish a risk scoring derived from potential risk factors (multivariable model) for hip preservation. Eight variables were identified to be strongly correlated with a decreased rate of hip survival post-therapy, and a comprehensive risk scoring was developed for predicting hip-preservation outcomes. The C-index stood at 0.72, and the areas under the receiver operating characteristics for the risk score's 5- and 10-year hip failure event predictions were 0.74 and 0.72, respectively. This risk score outperforms conventional methods in forecasting hip preservation. Bone grafting shows sustained benefits in treating ONFH when applied under the right indications. Furthermore, the risk scoring proves valuable as a decision-making tool, facilitating risk stratification for ONFH treatments in future.

Unraveling the Role of Endothelial Dysfunction in Osteonecrosis of the Femoral Head: A Pathway to New Therapies.

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.

A New Automated Prognostic Prediction Method Based on Multi-Sequence Magnetic Resonance Imaging for Hepatic Resection of Colorectal Cancer Liver Metastases.

Colorectal cancer is a prevalent and life-threatening disease, where colorectal cancer liver metastasis (CRLM) exhibits the highest mortality rate. Currently, surgery stands as the most effective curative option for eligible patients. However, due to the insufficient performance of traditional methods and the lack of multi-modality MRI feature complementarity in existing deep learning methods, the prognosis of CRLM surgical resection has not been fully explored. This paper proposes a new method, multi-modal guided complementary network (MGCNet), which employs multi-sequence MRI to predict 1-year recurrence and recurrence-free survival in patients after CRLM resection. In light of the complexity and redundancy of features in the liver region, we designed the multi-modal guided local feature fusion module to utilize the tumor features to guide the dynamic fusion of prognostically relevant local features within the liver. On the other hand, to solve the loss of spatial information during multi-sequence MRI fusion, the cross-modal complementary external attention module designed an external mask branch to establish inter-layer correlation. The results show that the model has accuracy (ACC) of 0.79, the area under the curve (AUC) of 0.84, C-Index of 0.73, and hazard ratio (HR) of 4.0, which is a significant improvement over state-of-the-art methods. Additionally, MGCNet exhibits good interpretability.

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.

MZB1 regulates cellular proliferation, mitochondrial dysfunction, and inflammation and targets the PI3K-Akt signaling pathway in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a pathological condition characterized by the premature release and activation of trypsinogens and other enzyme precursors. In severe cases, the mortality rates are in the range of 20-30% and may even be as high as 50%. Though various prophylaxes are available for AP, the mechanism of its progression is unclear. Marginal zone B and B-1 cell-specific protein 1 (MZB1) is found in the endoplasmic reticulum (ER) where it is expressed exclusively in the B cells there. MZB1 promotes proliferation, inhibits apoptosis, invasion, and inflammation, and mitigates mitochondrial damage in cells. However, the importance of MZB1 in AP has not yet been determined. METHODS: Differentially expressed genes (DEGs) between healthy pancreatic cells and those affected by AP were identified using datasets from Gene Expression Omnibus (GEO) datasets. Relative differences in MZB1 expression between normal and diseased tissues and cells were validated in vivo using a rat AP model induced with 4% (w/v) sodium taurocholate and in vitro using the AR42J rat pancreatic cell line exposed to caerulein (CAE). Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2`-deoxyuridine (EdU) assays were performed to detect and compare normal and pathological cell proliferation. Flow cytometry was employed to assess and compare cellular apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were applied to evaluate the apoptotic factors Bax and Bcl. The inflammatory factors interleukin (IL)-6 and IL-1ß were quantified using Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR techniques. Mitochondrial function was evaluated using assays for reactive oxygen species (ROS) and tetramethylrhodamine methyl ester (TMRM). WB and qRT-PCR were utilized to measure the expression levels of the PI3K-Akt signaling pathway, followed by a rescue experiment involving the inhibitor of wortmannin. RESULTS: MZB1 was upregulated in the AP cases screened from the GEO datasets, the rat AP model, and the AR42J cells exposed to CAE. Overexpression of MZB1 enhanced the growth and supressed the cell death of AR42J cells while also activating the PI3K-Akt signaling pathway. MZB1 knockdown led to mitochondrial dysfunction and exacerbated inflammation. The rescue experiment demonstrated that MZB1 enhanced proliferation and inhibited apoptosis, mitochondrial dysfunction, and inflammation in pancreatic cells through the PI3K-Akt pathway. CONCLUSIONS: AP cells and tissues exhibited markedly elevated levels of MZB1 expression compared to their healthy counterparts. MZB1 overexpression promoted proliferation and supressed apoptosis, mitochondrial dysfunction, and inflammation in pancreatic cells through the positive regulation of the PI3K-Akt signaling pathway.

Improving Anti-HIV activity and pharmacokinetics of enfuvirtide (T20) by modification with oligomannose.

Dendritic cells (DCs) play a pivotal role in controlling HIV-1 infections of CD4+ T cells. DC-SIGN, which is expressed on the surface of DCs, efficiently captures HIV-1 virions by binding to the highly mannosylated membrane protein, gp120, and then the DCs transport the virus to target T cells in lymphoid organs. This study explored the modification of T20, a peptide inhibitor of HIV-1 fusion, by conjugation of the N-terminus with varying sizes of oligomannose, which are DC-SIGN-specific carbohydrates, aiming to create dual-targeting HIV inhibitors. Mechanistic studies indicated the dual-target binding of the conjugates. Antiviral assays demonstrated that N-terminal mannosylation of T20 resulted in increased inhibition of the viral infection of TZM-b1 cells (EC50 = 0.3-0.8 vs. 1.4 nM). Pentamannosylated T20 (M5-T20) exhibited a stronger inhibitory effect on virus entry into DC-SIGN+ 293T cells compared with T20 (67% vs. 50% inhibition at 500 µM). M5-T20 displayed an extended half-life in rats relative to T20 (T1/2: 8.56 vs. 1.64 h, respectively). These conjugates represent a potential new treatment for HIV infections with improved antiviral activity and pharmacokinetics, and this strategy may prove useful in developing dual-target inhibitors for other pathogens that require DC-SIGN involvement for infection.

Surface display system of Bacillus subtilis: A promising approach for improving the stability and applications of cellobiose dehydrogenase.

Cellobiose dehydrogenase (CDH) plays a crucial role in lignocellulose degradation and bioelectrochemical industries, making it highly in demand. However, the production and purification of CDH through fungal heterologous expression methods is time-consuming, costly, and challenging. In this study, we successfully displayed Pycnoporus sanguineus CDH (psCDH) on the surface of Bacillus subtilis spores for the first time. Enzymatic characterization revealed that spore surface display enhanced the tolerance of psCDH to high temperature (80 °C) and low pH levels (3.5) compared to free psCDH. Furthermore, we found that glycerol, lactic acid, and malic acid promoted the activity of immobilized spore-displayed psCDH; glycerol has a more significant stimulating effect, increasing the activity from 16.86 ± 1.27 U/mL to 46.26 ± 3.25 U/mL. After four reuse cycles, the psCDH immobilized with spores retained 48% of its initial activity, demonstrating a substantial recovery rate. In conclusion, the spore display system, relying on cotG, enables the expression and immobilization of CDH while enhancing its resistance to adverse conditions. This system demonstrates efficient enzyme recovery and reuse. This approach provides a novel method and strategy for the immobilization and stability enhancement of CDH.

Identification of a family with van der Hoeve's syndrome harboring a novel COL1A1 mutation and generation of patient-derived iPSC lines and CRISPR/Cas9-corrected isogenic iPSCs.

Van der Hoeve's syndrome, also known as osteogenesis imperfecta (OI), is a genetic connective tissue disorder characterized by fragile, fracture-prone bone and hearing loss. The disease is caused by a gene mutation in one of the two type I collagen genes COL1A1 or COL1A2. In this study, we identified a novel frameshift mutation of the COL1A1 gene (c.1607delG) in a family with OI using whole-exome sequencing, bioinformatics analysis and Sanger sequencing. This mutation may lead to the deletion of a portion of exon 23 and the generation of a premature stop codon in the COL1A1 gene. To further investigate the impact of this mutation, we established two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of OI patients carrying a novel mutation in the COL1A1 gene. Osteoblasts (OB) derived from OI-iPSCs exhibited reduced production of type I collagen and diminished ability to differentiate into osteoblasts. Using a CRISPR-based homology-directed repair strategy, we corrected the OI disease-causing COL1A1 novel mutations in iPSCs generated from an affected individual. Our results demonstrated that the diminished expression of type I collagen and osteogenic potential were enhanced in OB induced from corrected OI-iPSCs compared to those from OI-iPSCs. Overall, our results provide new insights into the genetic basis of Van der Hoeve's syndrome and highlight the potential of iPSC technology for disease modeling and therapeutic development.

Case Report: In situ pulmonary artery thrombosis in a 12-year-old girl classified as systemic lupus erythematosus.

In situ pulmonary artery thrombosis (ISPAT) is a relatively rare but potentially life-threatening complication of systemic lupus erythematosus (SLE) in children. We report the case of a 12-year-old girl who presented with fever, chest pain, and dyspnea. Immune thrombocytopenia was identified due to purpura and menorrhagia 3 months before presentation with a lowest platelet count of 12 × 109/L. The sudden onset of fever, chest pain, and dyspnea were misdiagnosed as hyperinflammatory responses caused by pneumonia; these symptoms ameliorated with glucocorticoid and antibiotic treatment. The reappearance of symptoms after dose reduction of glucocorticoids and the observation of bloody bronchoalveolar lavage fluid necessitated further evaluation. Pulmonary artery thrombosis/embolism was identified using computed tomography pulmonary angiography and high D-dimer quantitative level of 4,118 µg/L (normal <252 µg/L). Ultrasonography of the deep and superficial veins of both lower limbs and renal veins revealed no thrombosis, suggesting the diagnosis of ISPAT. Further etiological evaluation revealed positive antinuclear antibodies, lupus anticoagulant, and anti-SSA antibodies, confirming SLE. Repeated normal urine analysis indicated that lupus nephritis was unlikely. Further, the negative anticardiolipin and anti-ß2 glycoprotein antibodies and temporary positive lupus anticoagulant suggested that antiphospholipid syndrome was unlikely. The patient received anticoagulants, glucocorticoids, hydroxychloroquine, and mycophenolate therapy. Her symptoms gradually improved, and she was discharged. At the 1-month follow-up, the thrombosis had resolved. During the 1-year follow-up, her condition remained well without SLE relapse. Our experience with this case emphasizes searching for SLE in the case of ISPAT and pulmonary hemorrhages. ISPAT can occur in children with SLE and may be caused by hyperinflammatory response during SLE flare.

Glycan-Modified Peptides for Dual Inhibition of Human Immunodeficiency Virus Entry into Dendritic Cells and T Cells.

Dendritic cells (DCs) play a crucial role in HIV-1 infection of CD4+ T cells. DC-SIGN, a lectin expressed on the surface of DCs, binds to the highly mannosylated viral membrane protein gp120 to capture HIV-1 virions and then transport them to target T cells. In this study, we modified peptide C34, an HIV-1 fusion inhibitor, at different sites using different sizes of the DC-SIGN-specific carbohydrates to provide dual-targeted HIV inhibition. The dual-target binding was confirmed by mechanistic studies. Pentamannose-modified C34 inhibited virus entry into both DC-SIGN+ 293T cells (52%-71% inhibition at 500 µM) and CD4+ TZM-b1 cells (EC50 = 0.7-1.7 nM). One conjugate, NC-M5, showed an extended half-life relative to C34 in rats (T1/2: 7.8 vs 1.02 h). These improvements in antiviral activity and pharmacokinetics have potential for HIV treatment and the development of dual-target inhibitors for pathogens that require the involvement of DC-SIGN for infection.