Stevens-Johnson syndrome and toxic epidermal necrolysis associated with immune checkpoint inhibitors: a systematic review.

Introduction: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare yet life-threatening adverse events associated with immune checkpoint inhibitors (ICIs). This systematic review synthesizes the current literature to elucidate the clinical characteristics and outcomes of patients with ICI-related SJS/TEN. Methods: We conducted a thorough search across databases including Embase, Web of Science, Cochrane, MEDLINE, Scopus, and PubMed. Selection criteria focused on reports of SJS/TEN among cancer patients treated with ICIs, analyzing clinical manifestations, therapeutic interventions, and outcomes. Results: Our analysis included 47 articles involving 50 patients with ICI-related SJS/TEN. The cohort had a mean age of 63 years, with a slight male predominance (54%). Most patients had melanoma or non-small cell lung cancer. SJS/TEN typically occurred early, with a median onset of 23 days post-ICI initiation. Treatment primarily involved systemic corticosteroids and intravenous immunoglobulins. The overall mortality rate was 20%, higher for TEN at 32%, with infections and tumor progression as leading causes. Median time from onset to death was 28 days. Survivors experienced a median re-epithelization time of 30 days, positively correlated with the extent of epidermal detachment (rs = 0.639, p = 0.009). Deceased patients exhibited a significantly higher proportion of TEN (90% vs. 48%, p = 0.029) and a larger epidermal detachment area (90% vs. 30% of the body surface area [BSA], p = 0.005) compared to survivors. The combination therapy group showed a higher proportion of TEN compared to corticosteroid monotherapy or non-corticosteroid therapy groups (72% vs. 29% and 50%, p = 0.01), with no significant differences in mortality or re-epithelization time. Dual ICI therapy resulted in a higher TEN rate than single therapy (100% vs. 50%, p = 0.028). Among single ICI therapies, the sintilimab-treated group trended towards a higher TEN rate (75% vs. 40-50%, p = 0.417), a larger detachment area (90% vs. 30-48% of BSA, p = 0.172), and a longer re-epithelization time (44 vs. 14-28 days, p = 0.036) compared to other ICI groups, while mortality rates remained similar. Conclusion: ICI-related SJS/TEN substantially impacts patient outcomes. Prospective clinical trials are critically needed to further clarify the pathogenesis and optimize therapeutic regimens.

Comparison of efficacy and safety between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma.

Aims and objectives: The purpose of this study was to compare efficacy and side effects between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma (IH). Material and methods: This was a single center randomized controlled prospective study, all participants were firstly diagnosed with IH between August 2022 and January 2023 in our hospital and without any treatment before. Patients were randomized into two groups. PRO group: oral propranolol (2 mg/kg/day) continued for 6 months; PRO + LAU group: oral propranolol (2 mg/kg/day) for 6 months and intralesional injection of lauromacrogol for 2-4 times within 6 months. The dimensions, color, consistency, photographic documentation were well recorded based on Visual Analogue Scale (VAS) before and after starting treatment. According to the treatment response after 6 months, the results were classified into four levels: Grade 1, complete resolution achieved; Grade 2, with ≥50% reduction in size of IH; Grade 3, with <50% reduction in size of IH; Grade 4, no response or worsening of IH. Results: A total of 67 patients were involved in the study (17 boys, 50 girls; mean age, 3.6 months, range, 1.1-7.2 months) and randomized to receive oral propranolol combined with or without intralesional injection of lauromacrogol (29 in PRO group, 38 in PRO + LAU group). All patients completed treatment. Eleven patients (37.9%) in PRO group were in Grade 1, 14 patients (48.3%) in Grade 2, 4 patients (13.8%) in Grade 3, compared with these in PRO + LAU group, 11 patients (28.9%) in Grade 1, 24 patients (63.2%) in Grade 2, and 3 patients (7.9%) in Grade 3. No patient was in Grade 4, and no severe side effects were observed in both group. In PRO group, it takes an average of 17.1 ± 5.4 weeks from the start of treatment to cure, and in PRO + LAU group, the average time is 13.7 ± 4.9 weeks. Conclusion: Oral propranolol with intralesional injection of lauromacrogol was a safety treatment strategy for IH. But it was not superior to oral propranolol in final cure rates (P = 0.45), moreover, it cannot certainly offer the benefits of shortening the duration of oral drug treatment (P = 0.24).

Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study.

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

Mercury sources, transport, and transformation in rainfall-runoff processes: Mercury isotope approach.

Mercury (Hg) in runoff water poses significant ecological risks to aquatic ecosystems that can affect organisms. However, accurately identifying the sources and transformation processes of Hg in runoff water is challenging due to complex natural conditions. This study provides a comprehensive investigation of Hg dynamics in water from rainfall to runoff. The Hg isotope fractionation in water was characterized, which allows accurate quantification of Hg sources, transport, and transformations in rainfall-runoff processes. Δ200Hg and corrected Δ199Hg values can serve as reliable tracers for identifying Hg sources in the runoff water and the variation of δ202Hg can be explained by Hg transformation processes. During runoff migration processes, Hg from rainfall is rapidly absorbed on the land surface, while terrestrial Hg entering the water by the dissolution process becomes the primary component of dissolved mercury (DHg). Besides the dissolution and adsorption, microbial Hg(II) reduction and demethylation of MeHg were dominant processes for DHg in the runoff water that flows through the rice paddies, while photochemical Hg(II) reduction was the dominant process for DHg in the runoff water with low water exchange rates. Particulate Hg (PHg) in runoff water is dominantly originated by the terrestrial material and derived from the dissolution and adsorption process. Tracking sources and transformations of Hg in runoff water during the rainfall-runoff process provides a basis for studying Hg pollution in larger water bodies under complex environmental factors.

Ancient genomic analysis of a Chinese hereditary elite from the Northern and Southern Dynasties.

China's Northern and Southern Dynasties period (3rd-6th centuries AD) marked a significant era of ethnic integration in northern China. However, previous ancient DNA studies have primarily focused on northern ethnic groups, with limited research on the genetic formation of the hereditary elite family, especially considering their abundant archaeological record and clear material identity. In this study, we obtained the ancient genome of a hereditary elite family, Gao Bin (, 503-572 AD), at 0.6473-fold coverage with 475132 single-nucleotide polymorphisms (SNPs) on the 1240k panel. His mitochondrial haplogroup belonged to Z4 and Y-haplogroup to O1a1a2b-F2444*. The genetic profile of Gao Bin was most similar to that of the northern Han Chinese. He could be modelled as deriving all his ancestry from Late Neolithic to Iron Age Yellow River farmers without influence from Northeast Asia, Korea, or the Mongolian Plateau. Our study sheds light on the genetic formation of hereditary elite families in the context of the Southern and Northern Dynasties ethnic integration.

Ancient genomes illuminate the demographic history of Shandong over the past two millennia.

Shandong province, located in the Lower Yellow River, is one of the birthplaces of ancient Chinese civilization. However, the comprehensive genetic histories of this region have remained largely unknown until now due to a lack of ancient human genomes. Here, we present 21 ancient genomes from Shandong dating from the Warring States period to the Jin-Yuan Dynasties. Unlike the early Neolithic samples from Shandong, the historical samples are most closely related to post-Late Neolithic populations of the Middle Yellow River Basin, suggesting a population turnover in Shandong from the Neolithic Age to the Historical era. In addition, we detect a close genetic affinity between the historical samples in Shandong and present-day Han Chinese, showing long-term genetic stability in Han Chinese at least since the Warring States period.

Reducing the degree of crosslinking of peptidoglycan in Listeria monocytogenes promoted the secretion of membrane vesicles.

Listeria monocytogenes (LM) is a Gram-positive (G+) bacterium that secretes nanoscale membrane vesicles (MVs). LM MVs comprise various bacterial components and may have potential as an antigen or drug-delivery vehicle; however, the low yield of the LM MVs limits related research. G+-bacterial MVs germinate from the bacterial plasma membrane and must pass through a thick crosslinked peptidoglycan layer for release. Herein, we aimed to increase the release of MVs by reducing the degree of crosslinking of peptidoglycan. We knocked out two genes related to the longitudinal crosslinking of peptidoglycan, dal and dat, and supplemented the knocked-out dal gene through plasmid expression to obtain a stably inherited recombinant strain LMΔdd::pCW633. The structure, particle size, and main protein components of MVs secreted by this recombinant strain were consistent with those secreted from the wild strain, but the yield of MVs was considerably increased (p < 0.05). Furthermore, Listeria ivanovii (LI) was found to secrete MVs that differed in the composition of the main proteins compared with those of LM MVs. The abovementioned method was also feasible for promoting the secretion of MVs from the attenuated LM strain and LI wild-type and attenuated strains. Our study provides a new method to increase the secretion of MVs derived from Listeria that could be extended to other G+ bacteria.

Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease.

Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand-receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.

MAZ-mediated up-regulation of BCKDK reprograms glucose metabolism and promotes growth by regulating glucose-6-phosphate dehydrogenase stability in triple-negative breast cancer.

Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.

3D E-textile for Exercise Physiology and Clinical Maternal Health Monitoring.

Electronic textiles (E-textiles) offer great wearing comfort and unobtrusiveness, thus holding potential for next-generation health monitoring wearables. However, the practical implementation is hampered by challenges associated with poor signal quality, substantial motion artifacts, durability for long-term usage, and non-ideal user experience. Here, we report a cost-effective E-textile system that features 3D microfiber-based electrodes for greatly increasing the surface area. The soft and fluffy conductive microfibers disperse freely and securely adhere to the skin, achieving a low impedance at the electrode-skin interface even in the absence of gel. A superhydrophobic fluorinated self-assembled monolayer was deposited on the E-textile surface to render it waterproof while retaining the electrical conductivity. Equipped with a custom-designed motion-artifact canceling wireless data recording circuit, the E-textile system could be integrated into a variety of smart garments for exercise physiology and health monitoring applications. Real-time multimodal electrophysiological signal monitoring, including electrocardiogram (ECG) and electromyography (EMG), was successfully carried out during strenuous cycling and even underwater swimming activities. Furthermore, a multi-channel E-textile was developed and implemented in clinical patient studies for simultaneous real-time monitoring of maternal ECG and uterine EMG signals, incorporating spatial-temporal potential mapping capabilities.

Loss-of-function mutations in Keratin 32 gene disrupt skin immune homeostasis in pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP) is an inflammatory papulosquamous dermatosis, characterized by hyperkeratotic follicular papules and erythematous desquamative plaques. The precise pathogenic mechanism underlying PRP remains incompletely understood. Herein, we conduct a case-control study involving a cohort of 102 patients with sporadic PRP and 800 healthy controls of Han Chinese population and identify significant associations (P = 1.73 × 10-6) between PRP and heterozygous mutations in the Keratin 32 gene (KRT32). KRT32 is found to be predominantly localized in basal keratinocytes and exhibits an inhibitory effect on skin inflammation by antagonizing the NF-κB pathway. Mechanistically, KRT32 binds to NEMO, promoting excessive K48-linked polyubiquitination and NEMO degradation, which hinders IKK complex formation. Conversely, loss-of-function mutations in KRT32 among PRP patients result in NF-κB hyperactivation. Importantly, Krt32 knockout mice exhibit a PRP-like dermatitis phenotype, suggesting compromised anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli. This study proposes a role for KRT32 in regulating inflammatory immune responses, with damaging variants in KRT32 being an important driver in PRP development. These findings offer insights into the regulation of skin immune homeostasis by keratin and open up the possibility of using KRT32 as a therapeutic target for PRP.

A 52-week follow-up, multi-center, randomized, double-blinded comparison of efficacy and safety of two hyaluronic acid fillers for the treatment of moderate-to-severe nasolabial folds in Chinese population.

INTRODUCTION: To investigate the efficacy and safety of Cutegel® MAX (Cutegel) in the correction of moderate-to-severe nasolabial folds (NLFS) compared to Restylane® (Restylane, control). METHODS: This study was a 52-week, multicenter, randomized, double-blinded, active-controlled clinical trial. Qualified participants with moderate-to-severe NLFs were randomly assigned in a 1:1 ratio to receive Cutegel or Restylane. For the primary efficacy endpoint, the response rate was defined as the percentage of subjects exhibiting an improvement of at least one-point based on blinded evaluation of Wrinkle Severity Rating Scale (WSRS) at 24 weeks after injection. Other secondary efficacy endpoints and treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Of 340 subjects randomized, 317 completed the week 52 visit. In the per protocol set (PPS), the blinded evaluator-assessed response rates at week 24 were 81.17% for Cutegel versus 77.56% for Restylane (p = 0.327). The between-group treatment differences in response rates were 3.60% [95% confidence interval (CI) = (-5.39%, 12.60%)], which demonstrated the noninferiority of Cutegel. Other secondary efficacy endpoints supported this. No significant differences were observed in the occurrence of adverse events between the two groups. CONCLUSION: Similar to Restylane, Cutegel was effective and well tolerated in correcting moderate-to-severe NLFs among the Chinese population.

Nasolabial folds (NLFs) are among the early indicators of facial aging process. In the past, rhytidectomy has been considered a safe procedure, yet it continues to carry risks such as hematoma, skin necrosis, nerve injury, and infection. With the ongoing development of biomaterials including hyaluronic acid (HA), minimally invasive injection procedures for the aesthetic correction of NLFs have become the preferred choice in recent years. The widespread use of HA has resulted in the development of various types of commercial HA fillers, such as Cutegel and Restylane. It is well known that HA filler products produce varying effects, attributable to differences in their components and physical properties. Previous studies have established that Restylane is a safe and effective HA dermal filler for the correction of NLFs. However, there is a lack of studies on both the cosmetic results and safety data for Cutegel in the published literature. Therefore, a randomized, double-blinded, active-controlled clinical trial was conducted at seven Chinese hospitals to evaluate the efficacy and safety of Cutegel for the correction of moderate-to-severe NLFs, compared to the approved Restylane in China. Among the 340 randomized subjects, 170 subjects received Cutegel, and 169 subjects received Restylane. Both groups reported similar improvements in WSRS (the between-group treatment differences in response rates exceeded the prespecified noninferiority margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety profiles. In summary, Cutegel proved to be well tolerated and effective in this randomized, active-controlled clinical study, demonstrating its noninferiority to Restylane and validating its use as an alternative treatment for Chinese subjects with moderate-to-severe NLFs.

Myocardial perfusion impairment in children with Kawasaki disease: assessment with cardiac magnetic resonance first-pass perfusion.

Background: Kawasaki disease (KD) potentially increases the risk of myocardial ischemia. This study aimed to semi-quantitatively evaluate myocardial perfusion impairment using cardiac magnetic resonance (CMR) first-pass perfusion in children with KD and explore the association between coronary artery (CA) dilation and myocardial perfusion. Methods: From December 2018 to July 2021, 77 patients with KD (48 male, 5.71±2.80 years) and 37 age- and sex-matched normal controls (20 male, 6.19±3.32 years) who underwent CMR in West China Second University Hospital were enrolled in this cross-sectional study with prospective data collection. A total of 30 of these patients completed the follow-up CMR, with a median interval of 13 months. Myocardial perfusion parameters including perfusion index (PI) and maximum signal intensity (Max SI) were obtained through rest first-pass perfusion. The internal diameter of the CA was assessed via coronary magnetic resonance angiography (CMRA) to calculate the coronary Z score. The global and regional myocardial parameters among the subgroups were compared. Statistical analysis included one-way analysis of variance (ANOVA), Pearson's correlation, and multivariate linear regression. Results: The global Max SI and regional Max SI of all segments in patients with and without CA dilation decreased compared with those in controls (P=0.19 and P<0.001, respectively). The global PI of patients with CA dilation and regional PI in segments subtended by dilated CA were lower than that of controls (P=0.002 and P<0.001, respectively) and were negatively correlated with the Z score (global: r=-0.576; regional: r=-0.351, both P<0.001). Multivariate analysis revealed that the Z score was negatively associated with global PI in KD (ß=-0.409, P=0.02, model R2=0.170). The global Max SI of patients with and without CA dilation during the follow-up CMR decreased compared with that of the first CMR (42.18±9.84 vs. 34.48±8.24, P=0.02; 44.82±7.13 vs. 36.61±7.67, P=0.03, respectively). Conclusions: CMR myocardial first-pass perfusion imaging can semi-quantitatively evaluate impaired myocardial perfusion in KD patients. Not only patients with CA dilation and segments subtended by dilated CA but also those without CA dilation and segments subtended by non-dilated CA developed myocardial perfusion impairment, the severity of myocardial perfusion impairment is associated with the degree of CA dilation.

2D MXene/MBene Superlattice with Narrow Bandgap as Superior Electrocatalyst for High-Performance Lithium-Oxygen Battery.

Lithium-oxygen (Li-O2) battery with large theoretical energy density (≈3500 Wh kg-1) is one of the most promising energy storage and conversion systems. However, the slow kinetics of oxygen electrode reactions inhibit the practical application of Li-O2 battery. Thus, designing efficient electrocatalysts is crucial to improve battery performance. Here, Ti3C2 MXene/Mo4/3B2-x MBene superlattice is fabricated its electrocatalytic activity toward oxygen redox reactions in Li-O2 battery is studied. It is found that the built-in electric field formed by a large work function difference between Ti3C2 and Mo4/3B2-x will power the charge transfer at the interface from titanium (Ti) site in Ti3C2 to molybdenum (Mo) site in Mo4/3B2-x. This charge transfer increases the electron density in 4d orbital of Mo site and decreases the d-band center of Mo site, thus optimizing the adsorption of intermediate product LiO2 at Mo site and accelerating the kinetics of oxygen electrode reactions. Meanwhile, the formed film-like discharge products (Li2O2) improve the contact with electrode and facilitate the decomposition of Li2O2. Based on the above advantages, the Ti3C2 MXene/Mo4/3B2-x MBene superlattice-based Li-O2 battery exhibits large discharge specific capacity (17 167 mAh g-1), low overpotential (1.16 V), and superior cycling performance (475 cycles).

Energy level regulation of anions via hydrogen bond effects to construct a stable solid electrolyte interface for a high-stability lithium metal anode.

An intermolecular hydrogen bond between 2,5-dihydroxyterephthalic acid and the anions in the Li+ solvation shell is constructed to promote the formation of a LiF-rich SEI on a metallic Li electrode. Li metal batteries with improved cyclability (140 cycles under an N/P ratio of 4.9) and high capacity retention (90%) are eventually obtained.

J-shaped association of the triglyceride glucose-body mass index with new-onset diabetes.

The triglyceride glucose-body mass index (TyG-BMI) is a convenient and clinically significant indicator of insulin resistance. This study aims to investigate the correlation between TyG-BMI and the onset of new-onset diabetes and determine an optimal reflection point for TyG-BMI. An analysis was conducted on 1917 participants from the risk evaluation of cancers in Chinese diabetic individuals: a lONgitudinal (REACTION) study. Participants were categorized based on their TyG-BMI, and the relationship between TyG-BMI and the incidence of new-onset diabetes was explored through logistic regression models, smoothed curve fitting with restricted cubic spline, and a two-piecewise logistic regression model. The mean age of the participants was 57.60 ± 8.89 years, with 66.5% being females. The mean TyG-BMI was 223.3 ± 32.8. Ultimately, 137 individuals (7.1%) progressed to diabetes after three years. After adjusting for covariates, TyG-BMI exhibited a positive correlation with new-onset diabetes (odd ratios (OR) for each standard deviation increase = 1.330, 95% CI 1.110-1.595). The relationship between TyG-BMI and new-onset diabetes was non-linear, with a inflcetion point at 202.9. This study reveals a positive non-linear relationship between TyG-BMI and the risk of new-onset diabetes in Chinese middle-aged and elderly individuals. When TyG-BMI exceeds 202.9, there is a significantly heightened risk of new-onset diabetes. These findings offer valuable insights for preventing new-onset diabetes.

Enhancing immunogenicity and antiviral protection of inactivated porcine reproductive and respiratory syndrome virus vaccine in piglets.

OBJECTIVE: Porcine interferon-γ (poIFN-γ) and porcine granulocyte-macrophage colony-stimulating factor (poGM-CSF) are multifunctional cytokines that exhibit robust antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV). In this study, the immunoadjuvant effects of recombinant poIFN-γ-poGM-CSF fusion protein in inactivated PRRSV vaccine administered to piglets were assessed. ANIMALS: Twenty-eight 4-week-old specific pathogen-free piglets. METHODS: The experimental piglets were divided into control, highly pathologic PRRSV, PRRSV killed virus vaccine (KV), poIFN-γ-poGM-CSF, KV + 1.0 mg poIFN-γ-poGM-CSF, KV + 2.0 mg poIFN-γ-poGM-CSF, and KV + 4.0 mg poIFN-γ-poGM-CSF groups. A recombinant poIFN-γ-linker-poGM-CSF fusion gene was constructed via splicing by overlap extension PCR and prepared using an Escherichia coli expression system, after which its adjuvant activity in the context of PRRSV KV administration was assessed. RESULTS: This analysis revealed the successful construction of the poIFN-γ-linker-poGM-CSF fusion gene via splicing by overlap extension PCR, with recombinant poIFN-γ-linker-poGM-CSF successfully being prepared in E coli with a plasmid vector for expressing thioredoxin fusion proteins with an enterokinase site. Importantly, the coadministration of poIFN-γ-linker-poGM-CSF and PRRSV KV significantly increased neutralizing antibody titers, accelerated viral clearance, reduced clinical symptoms, and prevented highly pathogenic PRRSV infection. CLINICAL RELEVANCE: The recombinant poIFN-γ-poGM-CSF fusion protein is a promising candidate adjuvant for use in the context of swine immunization and viral challenge.

A Cross Talking between the Gut Microbiota and Metabolites of Participants in a Confined Environment.

Certain workplaces, like deep-sea voyages, subject workers to chronic psychological stress and circadian rhythm disorders due to confined environments and frequent shifts. In this study, participants lived in a strictly controlled confined environment, and we analyzed the effects of a confined environment on gut microbiota and metabolites. The results showed that living in confined environments can significantly alter both the gut microbiota and the gut metabolome, particularly affecting lipid metabolism pathways like glycerophospholipid metabolism. There was a significant reduction in the abundance of Faecalibacterium and Bacteroides, while Blautia, Bifidobacterium, and Collinsella showed significant increases. An association analysis revealed a strong correlation between changes in the gut microbiota and the metabolome. Four upregulated lipid metabolites may serve as biomarkers for damage induced by confined environments, and certain gut microbiota alterations, such as those involving Faecalibacterium and Bacteroides, could be potential psychobiotics or therapeutic targets for enhancing mental health in a confined environment.

A Case of Complex Giant Rhinophyma Treated With Cosmetic Surgery.

ABSTRACT: Rhinophyma leads to severe facial deformities and significant social pressure for patients. Patients often seek medical intervention due to cosmetic defects and functional impairments, such as nasal congestion and airway collapse. Currently, there are numerous treatment modalities for rhinophyma, each with distinct advantages and disadvantages, leading to a lack of consensus in nasal vegetation management. Severe thickening in the nasal area can obstruct breathing through external nasal valve blockage, necessitating appropriate management for relief. This article presents a case study involving severe rhinophyma with respiratory obstruction that was successfully treated using incomplete resection followed by reconstruction to restore normal nasal contour. This not only achieved an upright position for nasal columella but also improved nasal contour to achieve normal appearance levels while completely relieving respiratory tract obstruction and enhancing patients' ventilation function. This method is easily performed without requiring additional expensive equipment, making it economically feasible even in ordinary medical centers while enabling patients to achieve a high quality of life.

Structural identification of single boron-doped graphdiynes by computational XPS and NEXAFS spectroscopy.

Boron-doped graphdiyne (B-GDY) material exhibits an excellent performance in electrocatalysis, ion transport, and energy storage. However, accurately identifying the structures of B-GDY in experiments remains a challenge, hindering further selection of suitable structures with the most ideal performance for various practical applications. In the present work, we employed density functional theory (DFT) to simulate the X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectra of pristine graphdiyne (GDY) and six representative single boron-doped graphdiynes at the B and C K-edges to establish the structure-spectroscopy relationship. A notable disparity in the C 1s ionization potentials (IPs) between substituted and adsorbed structures is observed upon doping with a boron atom. By analyzing the C and B 1s NEXAFS spectra on energy positions, spectral widths, spectral intensities, and different spectral profiles, we found that the six single boron-doped graphdiyne configurations can be sensitively identified. Moreover, this study provides a reliable theoretical reference for distinguishing different single boron-doped graphdiyne structures, enabling accurate selection of B-GDY structures for diverse practical applications.