Search

Dynamic molecules with tunable chemical and physical properties in response to external stimuli hold great potential for applications in information storage, smart molecular machines, and biomimetics. Among them, supramolecular springs and spin-crossover (SCO) complexes can both undergo visible macroscopic changes under heat or light stimulation. In this study, we synthesized a trinuclear Fe(II)-SCO complex, [(R-L)FeII{Au(CN)2}2] (R1), using a chiral chelating ligand decorated with rotatable benzyl rings. The [FeAu2] trinuclear molecules form a 21-helical supramolecular chain via elastic Au∙∙∙Au contacts. Interestingly, the synergy between the multiple dynamic factors (SCO event, rotation of the rings, and flexibility in Au∙∙∙Au distance) endows the complex with multiple switchings in both magnetism and structure, as well as the most intriguing characteristic of giant and anisotropic "breathing" feature in thermal expansion within two distinct temperature regimes. Specifically, complex R1 undergoes two hysteretic magnetic transitions: a non-spin transition and an unsymmetric SCO transition. Both transitions are triggered/accompanied by the rotation of the benzyl rings. Correspondingly, reversible spring-like motions of the helical chains are observed in the two distinct temperature regimes. This work demonstrates a significant success in incorporating both SCO and spring-like motion in one system, paving the way for designing multifunctional dynamic materials for future devices., (© 2024 Wiley‐VCH GmbH.)

Histone lysine-specific demethylase 1 (LSD1) is hyperactive in breast cancer, which is associated with the metastasis of the tumor. Current irreversible LSD1 inhibitors are all synthesized by covalently binding to the flavin adenine dinucleotide cofactor, which often have side effects due to the high affinity for a variety of targets. Here, we identified isoforsythiaside (IFA), a natural phenylpropanoid glycoside isolated from Forsythia suspensa , as a novel covalent inhibitor of LSD1. The target ligand fishing technique and LC-MS/MS analysis identified that IFA could covalently bind to the Ser817 residue of LSD1 by α,β-unsaturated ketone moiety to block the amine oxidase-like domain of LSD1. Moreover, RBMS3/Twist1/MMP2, the downstream signaling pathway of LSD1, was activated after IFA treatment to inhibit the metastasis of MDA-MB-231 cells in vitro and in vivo . This study provided novel molecular templates for development of LSD1 covalence-binding inhibitor and laid a foundation for developing agents against breast carcinoma metastasis for targeting LSD1.

The coronavirus disease 2019 (COVID-19) pandemic has reminded us of human infections with the H7N9 virus and has raised questions related to the clinical and molecular pathophysiological diversity between the two diseases. Here, we performed a proteomic approach on sera samples from patients with H7N9-virus or SARS-CoV-2-virus infection and healthy controls. Compared to SARS-CoV-2, H7N9-virus infection caused elevated neutrophil concentrations, T cell exhaustion, and increased cytokine/interleukin secretion. Cell-type deconvolution and temporal analysis revealed that T cells and neutrophils could regulate the core immunological trajectory and influence the prognosis of patients with severe H7N9-virus infection. Elevated tissue-enhanced proteins combined with alterations of clinical biochemical indexes suggested that H7N9 infection induced more severe inflammatory organ injury and dysfunction in the liver and intestine. Further mechanical analysis revealed that the high concentration of neutrophils might impact the intestinal enterocyte cells through cytokine-receptor interaction, leading to intestinal damage in patients with H7N9-virus infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mechanical control is fundamental for cellular localization within a tissue, including for tumor-associated macrophages (TAMs). While the innate immune sensing pathways cGAS-STING and RLR-MAVS impact the pathogenesis and therapeutics of malignant diseases, their effects on cell residency and motility remain incompletely understood. Here, we uncovered that TBK1 kinase, activated by cGAS-STING or RLR-MAVS signaling in macrophages, directly phosphorylates and mobilizes Zyxin, a key regulator of actin dynamics. Under pathological conditions and in STING or MAVS signalosomes, TBK1-mediated Zyxin phosphorylation at S143 facilitates rapid recruitment of phospho-Zyxin to focal adhesions, leading to subsequent F-actin reorganization and reduced macrophage migration. Intratumoral STING-TBK1-Zyxin signaling was evident in TAMs and critical in antitumor immunity. Furthermore, myeloid-specific or global disruption of this signaling decreased the population of CD11b +  F4/80 + TAMs and promoted PD-1-mediated antitumor immunotherapy. Thus, our findings identify a new biological function of innate immune sensing pathways by regulating macrophage tissue localization, thus providing insights into context-dependent mitigation of antitumor immunity., (© 2024. The Author(s).)

Macrophages play a multifaceted role in cancer biology, with both pro-tumorigenic and anti-tumorigenic functions. Understanding the mechanisms underlying macrophage involvement in cancer progression is essential for the development of therapeutic strategies. Our study analyzed single-cell RNA sequencing data from 12 patients with liver cancer and identified a subpopulation of macrophages characterized by elevated expression of SPP1, which correlates with poor prognosis in liver cancer patients. These SPP1 + macrophages induce upregulation of tumor stemness through a vitronectin (VTN)-dependent paracrine mechanism. Mechanistically, VTN derived from SPP1 + macrophages promote integrin αvβ5/adenosine 5'-monophosphate-activated protein kinase (AMPK)/Yes-associated protein 1 (YAP1)/SYR-box transcription factor 4 (SOX4) signaling, mediating liver tumor stemness and progression. Conversely, CCL15 produced by liver cancer cells drives polarization of M0 macrophages toward an SPP1 + macrophage phenotype, establishing a positive feedback loop of macrophage-tumor stemness. Furthermore, the presence of SPP1 + macrophages confers chemoresistance in liver cancer, and inhibition of the macrophage-tumor feedback loop through targeting integrin αvβ5/YAP1 signaling sensitizes liver cancer cells to chemotherapy. Our study highlights the crucial role of SPP1 + macrophages in liver cancer progression, providing novel insights for clinical liver cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cancer neuroscience is an emerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating a bidirectional interaction between nerves and cancers. Notably, immune cells also contribute to this communication, forming a triangular relationship that influences protumor inflammation and the effectiveness of immunotherapy. This review delves into the intricate mechanisms connecting the PNS and tumors, focusing on how various immune cell types influence nerve‒tumor interactions, emphasizing the clinical relevance of nerve‒tumor and nerve‒immune dynamics. By deepening our understanding of the interplay between nerves, cancer, and immune cells, this review has the potential to reshape tumor biology insights, inspire innovative therapies, and improve clinical outcomes for cancer patients., Competing Interests: The authors declare they have no conflicts of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Because of the unique and superior optoelectronic properties, metal halide perovskites (MHPs) have attracted great interests in photocatalysis. Element doping strategy is adopted to modify perovskite materials to improve their photocatalytic performance. However, the contribution of bare doping-site onto photocatalytic efficiency, and the correlation between doping locations and activity have not yet to be demonstrated. This promoted us to explore the potential of A-site-doped MHPs for photocatalysis. Herein, we dope potassium (K+) into CsPbBr3 and first reveal that the occupied locations of K+ in CsPbBr3 is lattice incorporation rather than surface segregation, which would change from A-site substitution to interstitial site in lattice with the increase of K+ concentrations. Taking H2 evolution as a model reaction, photocatalytic activity of CsPbBr3 after K+ doping could be significantly improved ~11-fold with A-site substitution, which is superior to that of interstitial site doping. Moreover, other alkali metals including Li, Na, and Rb doping give the same results. The structure of photocatalysts during reaction confirmed the contribution of A-site doping onto enhanced photocatalytic activity. Mechanistic insights show it is a result of the relaxed residual lattice strain induced promoted charge-carriers dynamics and formed upward shifting of band after K+ A-site doping., (© 2024 Wiley‐VCH GmbH.)

Piezo1 plays a pivotal role in regulating bone remodeling and homeostasis and has emerged as a promising target for chemical intervention in disuse osteoporosis. Nevertheless, the development of small-molecule Piezo1 agonists is still in its infancy, and highly efficacious Piezo1 agonists are urgently required. In this study, by shedding light on the structural novelty of the canonical Piezo1 agonist Yoda1, we initiated a structural optimization campaign based on the (thiadiazol-2-yl)pyrazine scaffold. A deuterated compound 12a was identified to be the most potent candidate against Piezo1 with an EC 50 value of 2.21 μM, which was over 20-fold more potent than the reference Yoda1. This compound effectively activated Piezo1 and initiated Ca 2+ influx in MSCs and promoted MSC osteogenesis via activating the Ca 2+ -related Erk signaling pathway. Furthermore, compound 12a was found to alleviate disuse osteoporosis with a desirable safety profile in a HU (hindlimb-unloading) rat model, thus warranting it as a potential probe for further investigation.

Salivary gland neoplasms (SGNs) represent a group of human neoplasms characterized by a remarkable cytomorphologic diversity, which frequently poses diagnostic challenges. Accurate histologic categorization of salivary tumors is crucial to make precise diagnoses and guide decisions regarding patient management. Within the scope of this study, a computer-aided diagnosis model using Vision Transformer (ViT), a cutting-edge deep learning model in computer vision, has been developed to accurately classify the most prevalent subtypes of SGNs. These subtypes include pleomorphic adenoma, myoepithelioma, Warthin tumor, basal cell adenoma, oncocytic adenoma, cystadenoma, mucoepidermoid carcinoma, and salivary adenoid cystic carcinoma. The data set comprised 3046 whole slide images of histologically confirmed salivary gland tumors, encompassing nine distinct tissue categories. SGN-ViT exhibited impressive performance in classifying the eight salivary gland tumors, achieving an accuracy of 0.9966, an area under the receiver operating characteristic curve value of 0.9899, precision of 0.9848, recall of 0.9848, and an F1 score of 0.9848. When compared with benchmark models, SGN-ViT surpassed them in terms of diagnostic performance. In a subset of 100 whole slide images, SGN-ViT demonstrated comparable diagnostic performance to that of the chief pathologist while significantly reducing the diagnosis time, indicating that SGN-ViT held the potential to serve as a valuable computer-aided diagnostic tool for salivary tumors, enhancing the diagnostic accuracy of junior pathologists., Competing Interests: Disclosure Statement None declared., (Copyright © 2024. Published by Elsevier Inc.)

As an appendage of the skin, hair protects against ultraviolet radiation and mechanical damage and regulates body temperature. It also reflects an individual's health status and serves as an important method of expressing personality. Hair loss and graying are significant psychosocial burdens for many people. Hair is produced from hair follicles, which are exclusively controlled by the dermal papilla (DP) at their base. The dermal papilla cells (DPCs) comprise a cluster of specialized mesenchymal cells that induce the formation of hair follicles during early embryonic development through interaction with epithelial precursor cells. They continue to regulate the growth cycle, color, size, and type of hair after the hair follicle matures by secreting various factors. DPCs possess stem cell characteristics and can be cultured and expanded in vitro. DPCs express numerous stemness-related factors, enabling them to be reprogrammed into induced pluripotent stem cells (iPSCs) using only two, or even one, Yamanaka factor. DPCs are an important source of skin-derived precursors (SKPs). When combined with epithelial stem cells, they can reconstitute skin and hair follicles, participating in the regeneration of the dermis, including the DP and dermal sheath. When implanted between the epidermis and dermis, DPCs can induce the formation of new hair follicles on hairless skin. Subcutaneous injection of DPCs and their exosomes can promote hair growth. This review summarizes the in vivo functions of the DP; highlights the potential of DPCs in cell therapy, particularly for the treatment of hair loss; and discusses the challenges and recent advances in the field, from basic research to translational applications.

Aims: Through evolving a precise RNA nuclease, hpCas13d, we have successfully inhibited hypertrophic cardiomyopathy in a compound heterozygous model. However, further investigation is needed to assess the long-term therapeutic effects and safety profiles of hpCas13d treatment., Materials and Methods: AAV-hpCas13d[RQ] was subcutaneously injected into neonatal Myh6 RH/RQ mice. Sequential echocardiography analyses were conducted at 4 months and 12 months to evaluate the sustained therapeutic effects of hpCas13d. Electrocardiography was employed to assess cardiac arrhythmias, and mice were euthanized at 12 months. Quantification of Myh6 RQ degradation induced by hpCas13d[RQ] was performed using digital droplet PCR and cDNA sequencing. Histological analysis, RNA sequencing, and proteomic analyses were utilized to examine the inhibitory effects on pathological phenotypes and downstream signaling pathways. Biodistribution, tissue damage, and host immune response to AAV-hpCas13d[RQ] were assessed to evaluate long-term safety profiles., Key Findings: The allele-specific RNA degradation persisted for 12 months in AAV-hpCas13d[RQ]-treated Myh6 RH/RQ mice. Partial degradation of pathogenic Myh6 RQ transcripts proved adequate for the long-term inhibition of cardiac hypertrophy, arrhythmias, fibrosis, and cellular apoptosis in Myh6 RH/RQ mice. RNA sequencing and proteomic analyses revealed that hpCas13d[RQ] treatment impeded hypertrophy and fibrosis, mitochondrial dysfunction, and abnormalities in ion channels downstream of mutant Myh6. Prolonged treatment with AAV-hpCas13d from the neonatal stage did not induce significant tissue damage, liver toxicity, humoral responses, or cellular immune reactions against the AAV9 capsid and bacterial hpCas13d., Significance: These results underscore the promising translational potential of AAV-hpCas13d in treating cardiovascular diseases and advancing in vivo gene therapy., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024. Published by Elsevier Inc.)

It has long been widely acknowledged that ultraviolet (UV) light is an environment risk factor that can lead to cancer, particularly skin cancer. However, it is worth noting that UV radiation holds potential for cancer treatment as a relatively high-energy electromagnetic wave. With the help of nanomaterials, the role of UV radiation has caught increasing attention in cancer treatment. In this review, we briefly summarized types of UV-induced cancers, including malignant melanoma, squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma. Importantly, we discussed the primary mechanisms underlying UV carcinogenesis, including mutations by DNA damage, immunosuppression, inflammation and epigenetic alterations. Historically limited by its shallow penetration depth, the introduction of nanomaterials has dramatically transformed the utilization of UV light in cancer treatment. The direct effect of UV light itself generally leads to the suppression of cancer cell growth and the initiation of apoptosis and ferroptosis. It can also be utilized to activate photosensitizers for reactive oxygen species (ROS) production, sensitize radiotherapy and achieve controlled drug release. Finally, we comprehensively weigh the significant risks and limitations associated with the therapeutic use of UV radiation. And the contradictory effect of UV exposure in promoting and inhibiting tumor has been discussed. This review provides clues for potential clinical therapy as well as future study directions in the UV radiation field. The precise delivery and control of UV light or nanomaterials and the wavelength as well as dose effects of UV light are needed for a thorough understanding of UV radiation., (© 2024. The Author(s).)

Mild and inexpensive copper-catalyzed aromatization-driven ring-opening amination and oxygenation of spiro dihydroquinazolinones are presented, respectively. These protocols provide facile and atom-economical access to the aminated and the carbonyl-containing quinazolin-4(3H)-ones in good yields with good functional group compatibility, which are difficult to obtain by conventional methods. Remarkably, a telescoped procedure involving the condensation and the ring-opening/functionalization for simple cycloalkanone was found to be accessible. Mechanistic studies suggest a radical pathway for this transformation., (© 2024 Wiley-VCH GmbH.)

Background: The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients., Methods: A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors., Results: In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score <8; 74.10%), while daily exercise in recovery period (OR: 0.457, 95%CI: 0.229 ~ 0.913), a low-fat diet (OR: 0.600, 95%CI: 0.401 ~ 0.898) and the recovery time from 2 to 4 months (OR: 0.639, 95%CI: 0.445 ~ 0.918) were the protective factors., Conclusion: This is the first time to use the C19-YRSm scale to evaluate the health status in China. The study revealed prevalence of persistent symptoms within 120 days after Omicron onset., (© 2024. The Author(s).)

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, underscoring an urgent need for strategies that enable early detection and phenotypic classification. Here, we conducted a label-free surface-enhanced Raman spectroscopic (SERS) analysis of serum exosomes from 643 participants to elucidate the biochemical deregulation associated with LC progression and the unique phenotypes of different LC subtypes. Iodide-modified silver nanofilms were prepared to rapidly acquire SERS spectra with a high signal-to-noise ratio using 0.5 μL of patient exosomes. We performed interpretable and automated machine learning (ML) analysis of differential SERS features of serum exosomes to build LC diagnostic models, which achieved accuracies of 100% and 81% for stage I lung adenocarcinoma and its preneoplasia, respectively. In addition, the ML-derived exosomal SERS models effectively recognized different LC subtypes and disease stages to guide precision treatment. Our findings demonstrate that spectral fingerprinting of circulating exosomes holds promise for decoding the clinical status of LC, thus aiding in improving the clinical management of patients.

Background: Danon disease (DD) is a rare X-linked dominant lysosomal storage disorder. Studies on DD pediatric patients are limited due to the small number of cases and challenges in early detection., Methods: We retrospectively analyzed clinical and genetic data of 29 pediatric patients who visited our hospital for treatment or genetic counseling of DD from July 2014 to December 2023., Results: The mean age at diagnosis was 7.2±5.9 years for males (n=21) and 9.4±5.0 years for females (n=8). Asymptomatic elevated liver aminotransferase and/or creatine kinase (CK) levels were initial manifestations detected in 10 (48%) male patients and absent in female patients. Hypertrophic cardiomyopathy (HCM) was observed in 20 (95%) male and 7 (88%) female patients, while dilated cardiomyopathy (DCM) was not detected. Ventricular preexcitation (VP) was observed initially in 10 (36%) patients and in 15 (54%) at latest evaluation. Patients with VP had higher left ventricular posterior wall thickness in diastole z-scores than those without VP (5.6±2.2 vs. 3.5±2.1, p=0.029). During a median 2.7-years follow-up, two males received heart transplants. One boy and one girl died of heart failure and sudden cardiac arrest, respectively. Twenty-three pathogenic LAMP2 variants were identified, including seven novel variants., Conclusions: A retrospective review of 29 DD cases suggests an underrecognized asymptomatic period in male DD patients, characterized by elevations in serum CK and transaminases. HCM appears to be the only cardiac manifestation in pediatric female patients, unlike a high incidence of DCM in adult female patients. The incidence of VP may increase with disease progression., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To present a novel intraoperative application technique of basic salt solution (BSS) perfusate to address residual epiretinal perfluorocarbon liquid (PFCL) droplets., Methods: Following standard liquid-gas exchange and aspiration of visible PFCL using a flute needle, the adjuvant drip-irrigative method is employed. A 2mL needle containing BSS is introduced and maneuvered circumferentially around the posterior pole while injecting BSS intermittently to obviate droplet presence. Subsequently, droplets lying flat to the surface drain via the flute needle, and the process if repeated until no droplets are visible., Results: Among 112 consecutive patients diagnosed with rhegmatogenous retinal detachment (RDD) with at least 3 months follow-up, 109 patients (109 eyes, [97%]) experienced no PFCL-related complications follow pars plana vitrectomy. Among three patients with PFCL-related complications, two (2 eyes) presented with residual droplets on the retinal surface during silicone oil retrieval, and one (1 eyes) had PFCL migration to the anterior chamber. No patients experienced sub-retinal/ sub-foveal PFCL or iatrogenic injury., Conclusion: This adjuvant drip-irrigative technique offers enhanced droplet visibility, reduced risk of iatrogenic retinal damage, and ease of application. Findings reported suggest the potential of this approach as a standard practice when using PFCL to mitigate complications., (© 2024. The Author(s).)

Cancer-associated fibroblasts (CAFs) are known to play an important role in cancer progression, but their effects on tumor cell dormancy and the underlying mechanisms remain to be explored. Here, we aimed to dissect the intercellular communication between CAFs and oral squamous cell carcinoma (OSCC) cells under cellular dormancy. In this study, we investigated 61 OSCC patients and found that low expression of Differentiated Embryonic Chondrocyte gene 2 (DEC2) was closely associated with tumor recurrence, cisplatin chemotherapy administration, and infiltration of CAFs. Overexpression of DEC2 promoted the invasion and migration ability of OSCC cells but inhibited their proliferation and glucose metabolism, and characterized them as dormant and cisplatin-resistant cells. C-X-C motif ligand 1 (CXCL1) from CAFs was found to down-regulate DEC2 expression in OSCC cells, ultimately awakening dormant cells and leading to tumor recurrence, which was validated in vitro and in vivo . In conclusion, CAFs-derived CXCL1 downregulated DEC2 and "interrupted" DEC2-mediated OSCC cell dormancy, which may be a mechanism by which CAFs modulate OSCC cell dormancy and contribute to the development of new therapies for OSCC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To observe the clinical characteristics of fungal and Brucella infections of the lumbar spine and explore the key points for their differential diagnosis., Methods: The clinical data of 12 patients with fungal infection (the fungal group) and 31 patients with Brucella infection (the Brucella group) of the lumbar spine confirmed by microbiological culture and antigen test were retrospectively analysed. The differences in the clinical characteristics and imaging manifestations were observed between the two groups., Results: The peripheral blood neutrophil ratio, erythrocyte sedimentation rate, serum total protein and serum globulin levels in the fungal group were higher compared with the Brucella group, while the peripheral blood lymphocyte count, lymphocyte ratio and albumin-globulin ratio were lower in the fungal group compared with the Brucella group ( P < 0.05). As for imaging examinations, the proportion of bone destruction centred on the intervertebral disc with surrounding osteosclerosis on computed tomography (CT) imaging showed a statistical difference between the Brucella group and the fungal group ( P < 0.05). Fungal infection patients showed more osteosclerosis-free areas around the bone destruction on magnetic resonance imaging (MRI) than Brucella infection patients., Conclusion: There are certain similarities in clinical manifestations between fungal and Brucella infections of the lumbar spine, but the haematological indices and image features of CT and MRI can effectively differentiate between them, providing guidance for the clinical differential diagnosis., Competing Interests: The authors declare that they have no competing interests., (© 2024 Fu et al.)

Background: This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors., Methods: Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated., Results: A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55 μm to 278.31 ± 157.34 μm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p < 0.001). The mean number of intravitreal injections was 8.6 ± 5.4. The dry group (10 eyes, 40%) was more likely to have higher branching vascular network vessel density (BVN VD; p = 0.021), submacular haemorrhages (p = 0.011) but lack polyp-related serous pigmented epithelial detachment (PED) (p = 0.037)., Conclusions: Conbercept was effective in eyes with PCV at maintaining functional and anatomical improvement. Baseline characteristics, including BVN VD, the presence of polyps with serous PED and submacular haemorrhage, seemed to be related to the response to conbercept., (© 2024. The Author(s).)

A nephroureterectomy conventionally consists of two independent section, which will considerably prolong the operation time. We developed a novel surgical technique for robotic-assisted laparoscopic nephroureterectomy without re-docking in a single position and aimed to access the safety, feasibility, and efficiency of our novel surgical technique. From August 2021 to October 2023, 53 patients who received robotic-assisted laparoscopic nephroureterectomy were retrospectively enrolled in this study. 25 patients underwent traditional nephroureterectomy and 28 patients underwent single-position nephroureterectomy. The basic characteristics of the enroll patients, perioperative parameters, and oncological outcomes were gathered and compared between novel technique robotic surgery group and traditional surgery group. The basic characteristics between two groups had no significantly difference except for the proportion of anticoagulation therapy. The operation time in novel technique robotic surgery group was shorter than that in traditional robotic surgery group, although there was no significant difference (p = 0.403). Lymph-node dissection in novel technique robotic surgery group was obvious more common than that in traditional robotic surgery group (p = 0.037), while the incision length in novel technique robotic surgery group was obviously shorter than that in traditional robotic surgery group (p < 0.001). The oncological outcomes showed no difference between two groups. Compared with traditional robotic-assisted laparoscopic nephroureterectomy, the innovative surgical technique of robotic-assisted laparoscopic nephroureterectomy in a single position showed the advantages of less surgical time, streamlined lymph-node dissection, less trauma, and expedited postoperative recovery, which is worth promoting in clinical practice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

We developed a mild, rapid process employing AgF and thioamides to produce α,α-difluoromethylene amines efficiently. This method exhibited remarkable tolerance toward various functional groups present in N -sulfonylthioamides, thereby broadening the scope of difluoromethylene sulfonamides through a straightforward approach. Additionally, we applied this approach to synthesize various perfluoroalkyl amines, establishing practical synthetic routes for exploring these compounds in pharmaceutical chemistry and materials science.

Respiratory tract infections are the most common triggers for heart failure in elderly people. The healthy respiratory commensal microbiota can prevent invasion by infectious pathogens and decrease the risk of respiratory tract infections. However, upper respiratory tract (URT) microbiome in the elderly is not well understood. To comprehend the profiles of URT microbiota in the elderly, and the link between the microbiome and heart failure, we investigated the oropharyngeal (OP) microbiome of these populations in Heilongjiang Province, located in the North-East of China, a high-latitude and cold area with a high prevalence of respiratory tract infection and heart failure. Taxonomy-based analysis showed that six dominant phyla were represented in the OP microbial profiles. Compared with young adults, the OP in the elderly exhibited a significantly different microbial community, mainly characterized by highly prevalent Streptococcus , unidentified&#95;Saccharibacteria , Veillonella , unidentified&#95;Pre votellaceae , and Neisseria . While unidentified&#95;Prevotellaceae dominated in the young OP microbiome. There was competition for niche dominance between Streptococcus and member of Prevotellaceae in the OP. Correlation analysis revealed that the abundance of unidentified&#95;Saccharibacteria was positive, while Streptococcus was negatively correlated to age among healthy elderly. The bacterial structure and abundance in the elderly with heart failure were much like healthy controls. Certain changes in microbial diversity indicated the potential OP microbial disorder in heart failure patients. These results presented here identify the respiratory tract core microbiota in high latitude and cold regions, and reveal the robustness of OP microbiome in the aged, supplying the basis for microbiome-targeted interventions.IMPORTANCETo date, we still lack available data on the oropharyngeal (OP) microbial communities in healthy populations, especially the elderly, in high latitude and cold regions. A better understanding of the significantly changed respiratory tract microbiota in aging can provide greater insight into characteristics of longevity and age-related diseases. In addition, determining the relationship between heart failure and OP microbiome may provide novel prevention and therapeutic strategies. Here, we compared OP microbiome in different age groups and elderly people with or without heart failure in northeastern China. We found that OP microbial communities are strongly linked to healthy aging. And the disease status of heart failure was not a powerful factor affecting OP microbiome. The findings may provide basic data to reveal respiratory bacterial signatures of individuals in a cold geographic region., Competing Interests: The authors declare no conflict of interest.

Objective: Temporary hemiepiphysiodesis (TH) is a very common technique for coronal angular deformity of the knee in children, especially non-idiopathic. However, there is currently a dearth of comparative research on the hinge eight-plate (HEP) and traditional eight-plate (TEP). This study aimed to assess the clinical effectiveness and implant-related complication rates of TH using TEP and HEP for non-idiopathic coronal angular deformity, as well as to identify clinical factors affecting correction velocity., Methods: We retrospectively observed a consecutive series of patients with non-idiopathic coronal angular deformity of the knee who underwent TH using HEP or TEP and completed the deformity correction process from July 2016 to July 2022. According to the kind of eight plates, we divided those patients into the HEP group and the TEP treatment group. Relevant clinical factors, including the mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), screw divergence angle (SDA), angle of plate and screw (APS), hinge angle of HEP (HA), and the knee zone location of the lower extremity mechanical axis, were documented. Additionally, deformity correction velocity, complications, and clinical efficacy were assessed. Categorical variables were analyzed using the chi-squared test, Fisher exact test, or Wilcoxon test, while continuous variables were evaluated using the t-test or analysis of variance (ANOVA)., Results: There were 29 patients in the HEP treatment group (seven girls and 22 boys) and 33 patients (12 girls and 21 boys) in the TEP treatment group. In all, 91.86% (79/86 knees) of the genu angular deformities were completely corrected, 6.98% (6/86 knees) had the overcorrection condition, and 10.47% (9/86 knees) had screw loosening. The swayback HEP rate was 11.29% (7/62 HEPs), which was related to the screw loosening in the HEP group (p < 0.001). The overall correction velocities and screw divergence angle change speeds in the HEP group were all significantly faster than those in the TEP group (p < 0.05). The initial APS of the HEP implanted was higher than that of TEP (p < 0.01), and multisite changes of APS during deformity correction of the HEP group were smaller than that of the TEP group., Conclusion: HEP proved to be an appropriate device for TH for non-idiopathic coronal angular deformities of the knee with high correction velocity in children. Avoiding the occurrence of the swayback phenomenon may reduce the complications of HEP., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD., Competing Interests: Declaration of competing interest All authors have nothing to disclose relevant conflict of interest to the present work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care., Methods: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children., Results: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage., Conclusions: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms., (© 2024. The Author(s).)

Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections., (© 2024 Wiley‐VCH GmbH.)

Purpose: To investigate bilateral axial length (AL) growth patterns and interactions of myopic eyes in anisometropic children during unilateral orthokeratology (OK) treatment in their singularly myopic eyes (Eyes1), followed by bilateral treatment when their second eyes (Eyes2) developed myopia., Methods: This study enrolled 94 eyes from 47 anisometropes (20 males). All patients had undergone monocular OK treatment for > 1 year followed by binocular treatment for > 1 year. Axial growth of Eyes1 and Eyes2 during the first year of monocular treatment (Stage 1), average annual axial elongation during the monocular treatment period, and axial elongation during the first year of binocular treatment (Stage 2) were respectively termed: S1E1 and S1E2, Annual E1 and Annual E2, and S2E1 and S2E2. Associations between AL growth and age, sex, interval time, and ocular parameters were analysed using correlation and generalised estimating equation (GEE) analysis., Results: During the monocular period, Eyes1 showed less AL growth (S1E1: 0.05 ± 0.18 mm; Annual E1: 0.05 ± 0.21 mm) than Eyes2 (S1E2: 0.51 ± 0.24 mm; Annual E2: 0.52 ± 0.25 mm) (all p < 0.001). During the binocular period, there was no significant difference between S2E1 and S2E2(0.21 ± 0.14 mm v. 0.19 ± 0.17 mm, p = 0.951). Between monocular and binocular periods, Eyes1 had significantly higher S2E1 compared to S1E1 and Annual E1 (both p < 0.001), and Eyes2 had significantly lower S2E2 than S1E2 and Annual E2 (both p < 0.001). In the GEE model, spherical equivalent refraction (SER) and between periods interval time showed independently significant associations with AL growth after adjusting for age and sex., Conclusion: Orthokeratology can significantly control AL growth in unilateral myopia. AL growth of the initial myopic OK-treated eyes accelerated relative to the monocular period when contralateral eyes developed myopia and assumed OK treatment. During the binocular treatment phase, OK lenses showed moderate and comparable effects on AL retardation across both eyes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Non-alcoholic steatohepatitis (NASH) is a critical stage in the progression of non-alcoholic fatty liver disease (NAFLD), characterized by obvious inflammation and fibrosis. Because of its high incidence rate and serious consequences, NASH is becoming a global health problem. The influence of endotoxin translocation on NASH is receiving attention. As a traditional Chinese herb that effectively improves hepatic inflammation, Fructus Aurantii (Quzhou origin, FAQ) is widely used in the clinical treatment of NASH. However, the intervention mechanism of FAQ on reg3g and related endotoxin translocation remains unclear., Aim: To study the mechanism of the impact by which ileal regenerating family member 3 gamma (reg3g) deficiency and subsequent endotoxin translocation impact the progression of NASH; To elucidate the efficacy and mechanism of FAQ in the treatment of NASH., Methods: Clinical serum, ileal tissue, and dynamic NASH model-related analyses collectively confirmed that reg3g is a pivotal gene associated with NASH. Reg3g -/- mice were used to assess the impact of reg3g on liver injury, inflammation, and fibrosis, as well as the underlying mechanism involved. In vitro studies elucidated the regulatory effects of FAQ on reg3g, intestinal barrier function, and intestinal permeability. Subsequently, the efficacy of FAQ was investigated in NASH mouse models. Pathological examinations combined with Western blotting (WB), immunohistochemistry (IHC), and multiplex immunohistochemical (mIHC) analyses were used to evaluate the effects of FAQ on mucosal repair and barrier function. Transepithelial electrical resistance (TEER), fluorescein isothiocyanate-dextran 4 (FD-4) experiments, coupled with enzyme linked immunosorbent assay (ELISA) and chromogenic LAL endotoxin assay were used to confirm intestinal permeability and endotoxin translocation. The results of WB and mIHC reflected the levels of endotoxin recruitment and M1 macrophage polarization in the liver. Parameters such as body weight, transaminases, and cholesterol were utilized to assess the metabolic effects of FAQ., Results: Decreased expression of reg3g was associated with the progression of NASH. Ileal deficiency in reg3g resulted in damage to the intestinal barrier and permeability, leading to the recruitment of endotoxins via the 'gut-liver' axis to the liver, causing the polarization of M1 macrophages, release of inflammatory factors, excessive inflammation, and activation of hepatic stellate cells (HSCs), leading to fibrosis. FAQ significantly upregulated ileal reg3g expression and the expression of intestinal barrier-related proteins tight junction protein 1 (ZO-1) and occludin (OLCN) in mice (p < 0.05), thereby improving intestinal barrier function and permeability. Reduced intestinal permeability led to decreases in endotoxins entering the bloodstream and accumulating in the liver (p < 0.05). The expression of CD68 suggested reduced polarization of M1 macrophages. Expression levels of actin alpha 2, smooth muscle actin (α-SMA) and extracellular matrix (ECM)-related proteins also decreased, indicating improved liver fibrosis., Conclusion: FAQ ameliorates NASH by upregulating the expression of reg3g. The upregulation of reg3g contributes to the repair of the intestinal barrier and permeability, reducing the recruitment of endotoxins and subsequent polarization of M1 macrophages, excessive inflammation, and fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objectives: To examine the association between latent profiles of multi-dimensional sleep characteristics and overweight/obesity (OWO) in Chinese preschool children., Study Design: The cross-sectional analysis included 3204 preschool children recruited from 24 kindergartens in Shanghai. Parents reported children's demographics and sleep characteristics, including sleep duration, timing and disturbances. Latent profile analysis (LPA) was used to identify sleep subtypes. Logistic regression models were used to evaluate the associations between sleep characteristics/subtypes and OWO., Results: Short sleep duration, late bedtime, long social jetlag and sleep disturbances were significantly associated with increased OWO. However, when considering the interplay of sleep duration and timing, there was no significant association between sleep duration and OWO for children sleeping later than 22:00. Three sleep subtypes were identified based on children's sleep duration, timing and disturbances: "Average Sleepers" (n = 2107, 65.8 %), "Good Sleepers" (n = 481, 15.0 %), and "Poor Sleepers" (n = 616, 19.2 %). "Good Sleepers" had reduced odds of being OWO (AOR, 0.72; 95 % CI, 0.56-0.93) compared to "Average Sleepers", while "Poor Sleepers" showed an increased risk of OWO (AOR, 1.36; 95 % CI, 1.11-1.67)., Conclusions: These findings highlight that improving multiple sleep characteristics simultaneously is a promising option to prevent and intervene childhood obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), the absence of licensed medications is striking. A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available medications. MASLD therapies center on four major pathways. Considering the close relationship between MASLD and type 2 diabetes, the first approach involves antidiabetic medications, including incretins, thiazolidinedione insulin sensitizers, and sodium-glucose cotransporter 2 inhibitors. The second approach targets hepatic lipid accumulation and the resultant metabolic stress. Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs. The third approach focuses on targeting oxidative stress, inflammation, and fibrosis. Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications., Competing Interests: JGF has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Background: Observational studies indicate a correlation between food intake and allergic rhinitis. The potential interplay between the immune system and allergic rhinitis might contribute causally to both food intake and allergic rhinitis, providing promising therapeutic avenues. However, elucidating the causal relationship and immune-mediated mechanisms between food intake and allergic rhinitis remains a pending task., Methods: We utilized a two-sample Mendelian randomization (MR) methodology to explore the causal relationship between food intake and allergic rhinitis. Furthermore, we investigated the potential causal relationship of immune cell signals with allergic rhinitis, as well as the potential causal relationship between food intake and immune cell signals. Moreover, employing both two-step Mendelian randomization and multivariable Mendelian randomization, we delved into the mediating role of immune cell signals in the causal relationship between food intake and allergic rhinitis. Leveraging publicly accessible genetic datasets, our analysis encompassed 903 traits, comprising 171 food intake features, 731 immune cell features, and one trait related to allergic rhinitis., Result: We found causal relationships between seven types of food intake and allergic rhinitis, as well as between 30 immune cell phenotypes and allergic rhinitis. Furthermore, our two-step Mendelian randomization analysis and multivariable Mendelian randomization analysis indicate that immune cells do not mediate the causal relationship between food intake and allergic rhinitis., Conclusion: To the best of our knowledge, we are the first to incorporate a large-scale dataset integrating immune cell features, food intake features, and allergic rhinitis into Mendelian randomization analysis. Our research findings indicate that there are causal relationships between six types of food intake and allergic rhinitis, as well as between 30 immune cell phenotypes and allergic rhinitis. Additionally, immune cells do not mediate these relationships., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Bao, Song, Song, Wang and Zhu.)

Objective: To explore establishment and finite element analysis of personalized proximal clavicular anatomical plate screw fixation model., Methods: A 40-year-old male healthy volunteer was selected and the finite element analysis modules of 3D reconstruction software Mimics 15.01, Hypermesh 2019 and Abaqus 2020 were used. The finite element model of anatomic plate at the proximal clavicle was established, and a vertical load of 250 N was applied to the distal end of long axis of clavicle about 15 mm, then the overall structure, plate and screw displacement cloud image, Mises stress distribution were observed., Results: The displacement distribution of the overall structure shows the maximum displacement was distributed on the distal clavicle. Under the four conditions of normal upper limb weight, longitudinal clavicle fracture, oblique fracture and shoulder impact violence during fall, longitudinal clavicle fracture and oblique fracture, the maximum displacement were 1.04 mm, 1.03 mm, 1.35 mm and 1.33 mm, respectively. The displacement cloud map of titanium alloy steel plate showed the largest displacement was distributed near the distal clavicular bone, and the maximum displacement were 0.89 mm, 0.88 mm, 1.10 mm and 1.09 mm, respectively. The displacement cloud map of titanium alloy screw showed the largest displacement was distributed at the root of the distal screw, and the maximum displacement were 0.88 mm, 0.87 mm, 1.08 mm and 1.06 mm, respectively. Mises stress distribution showed the maximum stress was mainly distributed on titanium alloy plates and screws, and the stress on the clavicle was very small. Mises stress distribution cloud showed the maximum Mises stress was distributed at the second row of screw holes near the clavicle, and the maximum Mises stress were 673.1, 678.1, 648.5, 654.4 MPa, respectively. The maximum stresses of titanium alloy screws were 414.5, 417.4, 415.8 and 419.7 MPa, respectively., Conclusion: The biomechanical changes of personalized proximal clavicular anatomical plates are demonstrated by using 3D finite element method to provide biomechanical data for personalized proximal clavicular anatomical plates.

Pyroptosis, a pro-inflammatory form of programmed cell death, is crucial for host defense against pathogens and danger signals. Proteolytic cleavage of gasdermin proteins B-E (GSDMB-GSDME) is well established as a trigger for pyroptosis, but the intracellular activation mechanism of GSDMA remains elusive. Here, we demonstrate that severe starvation induces pyroptosis through phosphorylation-induced activation of GSDMA. Nutrient stresses stimulate GSDMA activation via phosphorylation mediated by Unc-51-like autophagy-activating kinase 1 (ULK1). Phosphorylation of Ser353 on human GSDMA by ULK1 or the phospho-mimetic Ser353Asp mutant of GSDMA liberates GSDMA from auto-inhibition, facilitating its membrane targeting and initiation of pyroptosis. To further validate the significance of GSDMA phosphorylation, we generated a constitutively active mutant Ser354Asp of mouse Gsdma, which induced skin inflammation and hyperplasia in mice, reminiscent of phenotypes with activated Gsdma. This study uncovers phosphorylation of GSDMA as a mechanism underlying pyroptosis initiation and cellular response to nutrient stress., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

We report a novel visible-light-driven photoredox-catalyzed cascade reaction involving Conia-ene-type cyclization and Smiles rearrangement initiated from alkyne-tethered α-sulfonyl esters. This methodology not only facilitates the rapid synthesis of a broad spectrum of highly substituted methylenecarbocycles but also introduces a new mechanistic pathway with aryl group migration, surpassing the conventional 1,5-hydrogen shift typically observed in Conia-ene reactions.

Background: diabetices foot ulcer (DFU) are serious complications. It is crucial to detect and diagnose DFU early in order to provide timely treatment, improve patient quality of life, and avoid the social and economic consequences. Machine learning techniques can help identify risk factors associated with DFU development., Objective: The aim of this study was to establish correlations between clinical and biochemical risk factors of DFU through local foot examinations based on the construction of predictive models using automated machine learning techniques., Methods: The input dataset consisted of 566 diabetes cases and 50 DFU risk factors, including 9 local foot examinations. 340 patients with Class 0 labeling (low-risk DFU), 226 patients with Class 1 labeling (high-risk DFU). To divide the training group (consisting of 453 cases) and the validation group (consisting of 113 cases), as well as preprocess the data and develop a prediction model, a Monte Carlo cross-validation approach was employed. Furthermore, potential high-risk factors were analyzed using various algorithms, including Bayesian BYS, Multi-Gaussian Weighted Classifier (MGWC), Support Vector Machine (SVM), and Random Forest Classifier (RF). A three-layer machine learning training was constructed, and model performance was estimated using a Confusion Matrix. The top 30 ranking feature variables were ultimately determined. To reinforce the robustness and generalizability of the predictive model, an independent dataset comprising 248 cases was employed for external validation. This validation process evaluated the model's applicability and reliability across diverse populations and clinical settings. Importantly, the external dataset required no additional tuning or adjustment of parameters, enabling an unbiased assessment of the model's generalizability and its capacity to predict the risk of DFU., Results: The ensemble learning method outperformed individual classifiers in various performance evaluation metrics. Based on the ROC analysis, the AUC of the AutoML model for assessing diabetic foot risk was 88.48 % (74.44-97.83 %). Other results were found to be as follows: 87.23 % (63.33 %-100.00 %) for sensitivity, 87.43 % (70.00 %-100.00 %) for specificity, 87.33 % (76.66 %-95.00 %) for accuracy, 87.69 % (75.00 %-100.00 %) for positive predictive value, and 87.70 % (71.79 %-100.00 %) for negative predictive value. In addition to traditional DFU risk factors such as cardiovascular disorders, peripheral artery disease, and neurological damage, we identified new risk factors such as lower limb varicose veins, history of cerebral infarction, blood urea nitrogen, GFR (Glomerular Filtration Rate), and type of diabetes that may be related to the development of DFU. In the external validation set of 158 samples, originating from an initial 248 with exclusions due to missing labels or features, the model still exhibited strong predictive accuracy. The AUC score of 0.762 indicated a strong discriminatory capability of the model. Furthermore, the Sensitivity and Specificity values provided insights into the model's ability to correctly identify both DFU cases and non-cases, respectively., Conclusion: The predictive model, developed through AutoML and grounded in local foot examinations, has proven to be a robust and practical instrument for the screening, prediction, and diagnosis of DFU risk. This model not only aids medical practitioners in the identification of potential DFU cases but also plays a pivotal role in mitigating the progression towards adverse outcomes. And the recent successful external validation of our DFU risk prediction model marks a crucial advancement, indicating its readiness for clinical application. This validation reinforces the model's efficacy as an accessible and reliable tool for early DFU risk assessment, thereby facilitating prompt intervention strategies and enhancing overall patient outcomes., Competing Interests: We declare that we have no financial and personal relationships with other people ororganizations that can inappropriately influence our work, there is no professional orother personal interest of any nature or kind in any product, service and/or companythat could be construed as influencing the position presented in, or the review of,the manuscript entitled., (© 2024 The Authors.)

Objective: To establish a practical risk stratification system (RSS) based on ultrasonography (US) and clinical characteristics for predicting soft tissue masses (STMs) malignancy., Methods: This retrospective multicenter study included patients with STMs who underwent US and pathological examinations between April 2018 and April 2023. Chi-square tests and multivariable logistic regression analyses were performed to assess the association of US and clinical characteristics with the malignancy of STMs in the training set. The RSS was constructed based on the scores of risk factors and validated externally., Results: The training and validation sets included 1027 STMs (mean age, 50.90 ± 16.64, 442 benign and 585 malignant) and 120 STMs (mean age, 51.93 ± 17.90, 69 benign and 51 malignant), respectively. The RSS was constructed based on three clinical characteristics (age, duration, and history of malignancy) and six US characteristics (size, shape, margin, echogenicity, bone invasion, and vascularity). STMs were assigned to six categories in the RSS, including no abnormal findings, benign, probably benign (fitted probabilities [FP] for malignancy: 0.001-0.008), low suspicion (FP: 0.008-0.365), moderate suspicion (FP: 0.189-0.911), and high suspicion (FP: 0.798-0.999) for malignancy. The RSS displayed good diagnostic performance in the training and validation sets with area under the receiver operating characteristic curve (AUC) values of 0.883 and 0.849, respectively., Conclusion: The practical RSS based on US and clinical characteristics could be useful for predicting STM malignancy, thereby providing the benefit of timely treatment strategy management to STM patients., Critical Relevance Statement: With the help of the RSS, better communication between radiologists and clinicians can be realized, thus facilitating tumor management., Key Points: There is no recognized grading system for STM management. A stratification system based on US and clinical features was built. The system realized great communication between radiologists and clinicians in tumor management., (© 2024. The Author(s).)

Apoptosis, as type I cell death, is an active death process strictly controlled by multiple genes, and plays a significant role in regulating various activities. Mounting research indicates that the unique modality of cell apoptosis is directly or indirectly related to different diseases including cancer, autoimmune diseases, viral diseases, neurodegenerative diseases, etc. However, the underlying mechanisms of cell apoptosis are complicated and not fully clarified yet, possibly due to the lack of effective chemical tools for the nondestructive and real-time visualization of apoptosis in complex biological systems. In the past 15 years, various small-molecule fluorescent probes (SMFPs) for imaging apoptosis in vitro and in vivo have attracted broad interest in related disease diagnostics and therapeutics. In this review, we aim to highlight the recent developments of SMFPs based on enzyme activity, plasma membranes, reactive oxygen species, reactive sulfur species, microenvironments and others during cell apoptosis. In particular, we generalize the mechanisms commonly used to design SMFPs for studying apoptosis. In addition, we discuss the limitations of reported probes, and emphasize the potential challenges and prospects in the future. We believe that this review will provide a comprehensive summary and challenging direction for the development of SMFPs in apoptosis related fields.

Metamaterials have opened up a new field of electromagnetic wave stealth that can achieve cross-band electromagnetic wave stealth through high electromagnetic wave absorption and low infrared emission. However, traditional cross-band stealth metamaterials make covering the terahertz band challenging and have certain design flaws. This Letter introduces an innovative cross-band electromagnetic wave stealth metasurface design that can achieve cross-band stealth in the infrared, microwave, and THz bands. We use phase change materials and the gradient principle to achieve GHz and THz cross-band absorption. We also design surface height-covered low infrared emitting materials, which give them lower infrared emissivity. These functions give it enormous potential in military applications, and using phase change materials for cross-band absorption also provides new, to our knowledge, ideas for multifunctional stealth materials.

Phosphatidylethanolamine binding protein (PEBP) family plays important roles in multiple developmental processes in plants. In this study, a total of 11 PEBP gene family members were identified from the mango (Mangifera indica L.) genome, and these proteins were divided into three subfamilies based on their phylogenetic relationships: TERMINAL FLOWER 1 (TFL1)-like, MOTHER OF FT AND TFL (MFT)-like, and FLOWERING LOCUS T (FT)-like. Expression analysis revealed that MiFT1a, MiFT1b and MiFT2 were expressed mainly in leaves, whereas MiFT3 and MiFT4 were expressed mainly in embryos. The overexpression of MiFTs significantly promoted early flowering under both long- and short-day conditions. Interestingly, it still significantly promoted early flowering at 16 °C and 28 °C, with MiFT1a exhibiting the most significant, followed by MiFT1b and MiFT2. Additionally, the expression level of MiFT3 is related to the embryonic development of mango. Further studies revealed that overexpression of MiFT3 inhibited seed germination in transgenic Arabidopsis lines. In addition, the MiFT1a and MiFT1b transgenic lines did not respond to abiotic stress, while MiFT2, MiFT3 and MiFT4 enhanced resistance to salt or drought stress in Arabidopsis. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays revealed that MiFTs can interact with flower related and multiple stress proteins, such as bZIP protein (MiFD), 14-3-3 protein, zinc finger protein (MiZFP4), RING zinc-finger protein (MiRZFP34), and phosphatase 2C (MiPP2C25A and MiPP2C25B). These results indicate that FT subfamily not only regulates flowering but also participates in stress response, but there are differences in the function among these genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we devised a computational framework called Supervised Feature Learning and Scoring (SuperFeat) which enables the training of a machine learning model and evaluates the canonical cellular statuses/features in pathological tissues that underlie the progression of disease. This framework also enables the identification of potential drugs that target the presumed detrimental cellular features. This framework was constructed on the basis of an artificial neural network with the gene expression profiles serving as input nodes. The training data comprised single-cell RNA sequencing datasets that encompassed the specific cell lineage during the developmental progression of cell features. A few models of the canonical cancer-involved cellular statuses/features were tested by such framework. Finally, we illustrated the drug repurposing pipeline, utilizing the training parameters derived from the adverse cellular statuses/features, which yielded successful validation results both in vitro and in vivo. SuperFeat is accessible at https://github.com/weilin-genomics/rSuperFeat., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

A visible light-promoted aromatization-driven deconstructive fluorination of spiro carbocycles is presented. A series of spiro dihydroquinazolinones reacted efficiently with NFSI under visible light irradiation to afford the 2-(4-fluoroalkyl)quinazolin-4(3 H )-ones in good yields with excellent functional group tolerance. A radical pathway involving C-C bond cleavage and F atom transfer is proposed for the reaction. In addition, the ring-opening chlorination of spiro dihydroquinazolinones with NCS was also applicable.

Metal-organic frameworks (MOFs) have attained broad research attention in the areas of sensors, resistive memories, and optoelectronic synapses on the merits of their intriguing physical and chemical properties. In this review, recent progress on the synthesis of MOFs and their electronic applications is introduced and discussed. Initially, the crystal structures and properties of MOFs encompassing optical, electrical, and chemical properties are discussed in brief. Subsequently, advanced synthesis methods for MOFs are introduced, categorized into hydrothermal approach, microwave synthesis, mechanochemical synthesis, and electrochemical deposition. After that, the various roles of MOFs in widespread applications, including sensing, information storage, optoelectronic synapses, machine learning, and artificial intelligence, are discussed, highlighting their versatility and the innovative solutions they provide to long-standing challenges. Finally, an outlook on remaining challenges and a future perspective for MOFs are proposed.

Background: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear., Purpose: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides., Methods: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI + -MS, CETSA, immunoblot and SPR assay. The RAW264.7 Clec4G-RFP and RAW264.7 Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects., Results: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects., Conclusion: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction and Objectives: Fatty liver disease is a multisystem disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a more accurate indicator of chronic kidney disease (CKD) than nonalcoholic fatty liver disease (NAFLD). However, the relationship between recently defined metabolic dysfunction-associated steatotic liver disease (MASLD) and CKD is currently unclear. The objective of this cross-sectional study was to investigate the prevalence of CKD and albuminuria among individuals diagnosed with either MAFLD or MASLD., Patients and Methods: This study involved 5,492 participants who provided biochemical marker and liver ultrasound data from the U.S. National Health and Nutrition Examination Survey (2017-2020). Multiple logistic regression analyses were conducted to assess the independent associations of nonoverlapping MAFLD and MASLD with the presence of CKD or albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol)., Results: MAFLD and MASLD were identified in 47% and 44.5% of the participants, respectively. Individuals with MAFLD-only had a greater prevalence of CKD (24.7% vs. 8.3 %, P < 0.006) and albuminuria (18.6% vs. 5%, P < 0.01) than did those with MASLD-only. Importantly, after adjusting for factors such as sex, age, ethnicity, and alcohol use, it was demonstrated that individuals in the MAFLD-only group had a 4.73-fold greater likelihood of having prevalent CKD than those in the MASLD-only group (P < 0.03)., Conclusions: The MAFLD criteria better identify patients with CKD than do the MASLD criteria. Therefore, it is suggested that the MASLD criteria be reconsidered, as currently, the justification for changing from MAFLD to MASLD criteria may not be appropriate., Competing Interests: Conflicts of interest None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Study Objective: To prospectively investigate whether the application of vaginal repair (VR) of cesarean section scar defect (CSD) combined with a gonadotropin-releasing hormone agonist (GnRHa) achieve better clinical outcomes than VR alone., Design: A randomized clinical trial., Setting: University Hospital., Patients: A total of 124 women with CSD were undergoing expectant management from December 2016 to September 2021. 61 were randomized to VR+ GnRHa and 63 to VR alone., Intervention: Vaginal repair combined with GnRHa and vaginal repair alone., Measures and Main Results: The primary outcome was the duration of menstruation and thickness of the remaining muscular layer (TRM) at 6 months after surgery. Secondary outcomes included the length, width, and depth of the CSD; operation time; estimated blood loss; hospitalization time; and operative complications. Women were treated with either VR (n = 63) or VR + GnRHa (n = 61). Menstruation and TRM in patients pre vs post comparisons either with VR or VR + GnRHa are significantly improved (p <.05). Significant differences in menstruation duration and TRM occurred in patients treated with VR + GnRHa compared with those treated with VR (p <.05). Moreover, the rate of CSD after surgery in the VR group was significantly higher than that in the VR + GnRHa group (p = .033), and CSD patients in the VR + GnRHa group achieved better therapeutic effects than those in the VR group (p = .017). Patients who received VR + GnRHa had a shorter menstruation duration and a greater increment of TRM postoperatively than patients treated with VR alone (p = .021; p = .002, respectively)., Conclusion: VR + GnRHa therapy has a greater potential to improve scar healing and reduce the number of menstruation days than VR alone for symptomatic women with CSD., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH., Competing Interests: Declaration of competing interest All authors declare that there are no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)