The mechanism of extracellular CypB promotes glioblastoma adaptation to glutamine deprivation microenvironment.

Glioblastoma, previously known as glioblastoma multiform (GBM), is a type of glioma with a high degree of malignancy and rapid growth rate. It is highly dependent on glutamine (Gln) metabolism during proliferation and lags in neoangiogenesis, leading to extensive Gln depletion in the core region of GBM. Gln-derived glutamate is used to synthesize the antioxidant Glutathione (GSH). We demonstrated that GSH levels are also reduced in Gln deficiency, leading to increased reactive oxygen species (ROS) levels. The ROS production induces endoplasmic reticulum (ER) stress, and the proteins in the ER are secreted into the extracellular medium. We collected GBM cell supernatants cultured with or without Gln medium; the core and peripheral regions of human GBM tumor tissues. Proteomic analysis was used to screen out the target-secreted protein CypB. We demonstrated that the extracellular CypB expression is associated with Gln deprivation. Then, we verified that GBM can promote the glycolytic pathway by activating HIF-1α to upregulate the expression of GLUT1 and LDHA expressions. Meanwhile, the DRP1 was activated, increasing mitochondrial fission, thus inhibiting mitochondrial function. To explore the specific mechanism of its regulation, we constructed a si-CD147 knockout model and added human recombinant CypB protein to verify that extracellular CypB influenced the expression of downstream p-AKT through its cell membrane receptor CD147 binding. Moreover, we confirmed that p-AKT could upregulate HIF-1α and DRP1. Finally, we observed that extracellular CypB can bind to the CD147 receptor, activate p-AKT, and upregulate HIF-1α and DRP1 in order to promote glycolysis while inhibiting mitochondrial function to adapt to the Gln-deprived microenvironment.

TDDFT Study on the ESIPT Properties of 2-(2'-Hydroxyphenyl)-Benzothiazole and Sensing Mechanism of a Derived Fluorescent Probe for Fluoride Ion.

The level of fluoride ions (F-) in the human body is closely related to various pathological and physiological states, and the rapid detection of F- is important for studying physiological processes and the early diagnosis of diseases. In this study, the detailed sensing mechanism of a novel high-efficiency probe (PBT) based on 2-(2'-hydroxyphenyl)-benzothiazole derivatives towards F- has been fully investigated based on density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. F- attacks the O-P bond of PBT to cleavage the dimethylphosphinothionyl group, and the potential products were evaluated by Gibbs free energy and spectroscopic analyses, which ultimately identified the product as HBT-Enol1 with an intramolecular hydrogen bond. Bond parameters, infrared vibrational spectroscopy and charge analysis indicate that the hydrogen bond is enhanced at the excited state (S1), favoring excited state intramolecular proton transfer (ESIPT). The mild energy barrier further evidences the occurrence of ESIPT. Combined with frontier molecular orbital (FMO) analysis, the fluorescence quenching of PBT was attributed to the photoinduced electron transfer (PET) mechanism and the fluorescence turn-on mechanism of the product was attributed to the ESIPT process of HBT-Enol1.

Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy.

Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers. Despite the transformative impact of immunotherapy on cancer treatment, several outstanding challenges remain. These challenges include on-target off-tumor toxicity, systemic toxicity, and the complexity of achieving potent and sustainable therapeutic efficacy. Synthetic biology has emerged as a promising approach to overcome these obstacles, offering innovative tools for engineering living cells with customized functions. This review provides an overview of the current landscape and future prospects of cancer immunotherapy, particularly emphasizing the role of synthetic biology in augmenting its specificity, controllability, and efficacy. We delineate and discuss two principal synthetic biology strategies: those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits. This review concludes with a forward-looking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.

SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma.

Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. Patients with NF1 often have complications with tumors, such as neurofibroma. In order to investigate the pathogenesis of human neurofibroma, a systematic comparison of protein expression levels between Schwann cell-like sNF96.2 cells, which originated from malignant peripheral nerve sheath tumors (MPNST), and normal Schwann cells was performed using 4-D label-free proteomic analysis. In addition, the expression levels and localization of dysregulated proteins were confirmed using a Gene Expression Omnibus (GEO) transcriptomic dataset, Western blot analysis, and immunofluorescence labeling. The effects of SRY-box transcription factor 9 (SOX9) in the neurofibroma and surrounding microenvironment were evaluated in vivo using a tumor transplantation model. The present study observed that SOX9 and procollagen C-endopeptidase enhancer (PCOLCE) were significantly altered. NF1 mutation promoted the nuclear translocation and transcriptional activity of SOX9 in neurofibromas. SOX9 increased collagen VI secretions by enhancing the activation of PCOLCE in neurofibroma cells. These findings might provide new perspectives on the pathophysiological significance of SOX9 in neurofibromas and elucidate a novel molecular mechanism underlying neurofibromas.

Insights into the modulation of bacterial NADase activity by phage proteins.

The Silent Information Regulator 2 (SIR2) protein is widely implicated in antiviral response by depleting the cellular metabolite NAD+. The defense-associated sirtuin 2 (DSR2) effector, a SIR2 domain-containing protein, protects bacteria from phage infection by depleting NAD+, while an anti-DSR2 protein (DSR anti-defense 1, DSAD1) is employed by some phages to evade this host defense. The NADase activity of DSR2 is unleashed by recognizing the phage tail tube protein (TTP). However, the activation and inhibition mechanisms of DSR2 are unclear. Here, we determine the cryo-EM structures of DSR2 in multiple states. DSR2 is arranged as a dimer of dimers, which is facilitated by the tetramerization of SIR2 domains. Moreover, the DSR2 assembly is essential for activating the NADase function. The activator TTP binding would trigger the opening of the catalytic pocket and the decoupling of the N-terminal SIR2 domain from the C-terminal domain (CTD) of DSR2. Importantly, we further show that the activation mechanism is conserved among other SIR2-dependent anti-phage systems. Interestingly, the inhibitor DSAD1 mimics TTP to trap DSR2, thus occupying the TTP-binding pocket and inhibiting the NADase function. Together, our results provide molecular insights into the regulatory mechanism of SIR2-dependent NAD+ depletion in antiviral immunity.

Responsive Microgels through RAFT-HDA Dynamic Covalent Bonding Chemistry.

This paper developed a method for preparing ultrasound-responsive microgels based on reversible addition fragmentation chain transfer-hetero Diels-Alder (RAFT-HAD) dynamic covalent bonding. First, a styrene cross-linked network was successfully prepared by a Diels-Alder (DA) reaction between phosphoryl dithioester and furan using double-ended diethoxyphosphoryl dithiocarbonate (BDEPDF) for RAFT reagent-mediated styrene (St) polymerization, with a double-ended dienophile linker and copolymer of furfuryl methacrylate (FMA) and St as the dienophile. Subsequently, the microgel system was constructed by the HDA reaction between phosphoryl disulfide and furan groups using the copolymer of polyethylene glycol monomethyl ether acrylate (OEGMA) and FMA as the dienophore building block and hydrophilic segment and the polystyrene pro-dienophile linker as the cross-linker and hydrophobic segment. The number of furans in the dienophile chain and the length of the dienophile linker were regulated by RAFT polymerization to investigate the effects of the single-molecule chain functional group degree, furan/dithioester ratio, and hydrophobic cross-linker length on the microgel system. The prepared microgels can achieve the reversible transformation of materials under force responsiveness, and their preparation steps are simple and adaptive to various potential applications in biomedical materials and adaptive electrical materials.

A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease.

Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Aß accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.

Identification and verification of anoikis-related gene markers to predict the prognosis of patients with bladder cancer and assist in the diagnosis and treatment of bladder cancer.

Background: The recurrence and mortality rates of bladder cancer are extremely high, and its diagnosis and treatment are global concerns. The mechanism of anoikis is closely related to tumor metastasis. Methods: First, we obtained all the data needed for this study from a public database through a formal operational process. The data were then analyzed by bioinformatics technology. Through the limma package, we screened and obtained 313 anoikis-related genes [false discovery rate (FDR) <0.05, |log fold change (FC) | >0.585]. Then, through univariate independent prognostic analysis, we further screened 146 genes (P<0.05) related to the prognosis of bladder cancer from 313 differential genes. These 146 prognostically relevant differential genes were used for least absolute shrinkage and selection operator (LASSO) regression for further screening to obtain model-related genes and output model formulas. Through the nomogram, we can calculate the survival rate of patients more accurately. The accuracy of the nomogram was also confirmed by calibration curves, independent prognostic analysis, receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves. We then analysed the sensitivity of immunotherapy in bladder cancer patients with different risk scores via Tumor Immune Dysfunction and Exclusion (TIDE). Results: Through bioinformatics technology and public databases, a prognostic model including 9 anoikis-related genes (KLF12, INHBB, CASP6, TGFBR3, FASN, TPM1, OGT, RAC3, ID4) was obtained. Integrating risk scores with clinical information, we obtained a nomogram that can accurately predict patient survival. By querying the immunohistochemical results of the Human Protein Atlas database, two of the nine model-related genes (FASN, RAC3) have the value of further research and are expected to become new biomarkers to assist the diagnosis and treatment of bladder cancer. Through immune-related analysis, we found that patients in the low-risk group appeared to be more suitable for immunotherapy, while drug sensitivity analysis showed that bladder cancer patients in the high-risk group were more sensitive to common chemotherapy drugs. Conclusions: In this study, a prognostic model that can accurately predict the prognosis of patients with bladder cancer was constructed. FASN and RAC3 are expected to become a new biomarker for the diagnosis and treatment of bladder cancer.

Multiomics combined with single-cell analysis shows that mitophagy-related genes could accurately predict the prognosis of patients with clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a heterogeneous tumor that accounts for a large proportion of kidney cancer, It is prone to recurrence and metastasis, and has a high mortality rate. Although mitophagy is important for metastasis and the recurrence of various tumors, its effect on renal clear cell carcinoma is poorly understood. Methods: Mitophagy-related genes were obtained through the GeneCards database. We normalised the data from different sources by removing the batch effect. Next, we conducted a preliminary screening of mitophagy-related genes and obtained prognosis-related genes from differentially expressed genes. We constructed a prognostic model using least absolute shrinkage and selection operator (LASSO) regression with data from The Cancer Genome Atlas (TCGA) and GSE29609 datasets and validated it internally. International Cancer Genome Consortium (ICGC) and E-MTAB-1980 cohorts also provided double external validation. In addition, we combined multi-omics and single-cell data to comprehensively analyse mitophagy-related gene model signature (MRGMS). Combined with the mitophagy-related gene model (MRGM) score, we constructed a nomogram. Finally, we performed pathway enrichment analysis using a variety of methods. Results: Multiomics and single-cell data analysis showed that the MRGMS is important for patients with ccRCC and is expected to become a new biomarker. The construction of a nomogram was conducive to accurately predicting patient survival. Conclusions: Mitophagy-related genes are important for predicting the prognosis of ccRCC and are conducive to the development of more personalised treatment plans for patients.

Fluorescence emission mechanism for the π-conjugated zwitterion 2,4-Bisimidazolylphenol base on ESIPT: A TDDFT theoretical reconsideration.

Molecules with zwitterionic characteristics exhibit significant potential for utilization in nonlinear optics, optoelectronics, and organic lasers owing to their large dipole moments. Recently, the synthesized compound 2,4-bis (4,5-diphenyl-1H-imidazol-2-yl) phenol (2,4-bImP) by Sakai et al. has been noticed for its unique photochromic properties in solvents [J. Phys. Chem. A, 125 (2021), 4784-4792]. The observed fluorescence in chloroform was attributed to the keto tautomer. Based on the excited state intramolecular proton transfer, the photochromism of 2,4-bImP in chloroform was interpreted as zwitterion production. However, the zwitterion with a specific electronic structure can be in resonance with the conventional neutral structure. The impact of the resonance contribution from the zwitterion and the conventional neutral structure on fluorescence attribution was not taken into account in the previous studies. In this investigation, the ESIPT mechanism of the 2,4-bImP in chloroform has been explored using both the density functional theory and the time-dependent density functional theory. The optimized geometric configuration parameters illustrate the molecular resonant properties. The calculated fluorescence spectra on the basis of the optimization results further corroborate that the fluorescence peaks after proton transfer originates from the resonance of the zwitterionic and the neutral configuration. The zwitterionic nature of the molecule was demonstrated by electrostatic potential and atomic dipole modified Hesfeld atomic charge (ADCH) analysis. Furthermore, the characterization of potential energy curves and IR spectrum further verified the resonance of both the zwitterionic and neutral structures. The results reveal that the 2,4-bImP molecule generates the neutral o-quinoid structure and the zwitterionic structure resonance phenomenon following ESIPT. The aforementioned resonance structure offers novel insights into the ascription of fluorescence. These discoveries establish the theoretical foundation for the exploration and development of zwitterions.

Chronic hypoxia impairs skeletal muscle repair via HIF-2α stabilization.

BACKGROUND: Chronic hypoxia and skeletal muscle atrophy commonly coexist in patients with COPD and CHF, yet the underlying physio-pathological mechanisms remain elusive. Muscle regeneration, driven by muscle stem cells (MuSCs), holds therapeutic potential for mitigating muscle atrophy. This study endeavours to investigate the influence of chronic hypoxia on muscle regeneration, unravel key molecular mechanisms, and explore potential therapeutic interventions. METHODS: Experimental mice were exposed to prolonged normobaric hypoxic air (15% pO2, 1 atm, 2 weeks) to establish a chronic hypoxia model. The impact of chronic hypoxia on body composition, muscle mass, muscle strength, and the expression levels of hypoxia-inducible factors HIF-1α and HIF-2α in MuSC was examined. The influence of chronic hypoxia on muscle regeneration, MuSC proliferation, and the recovery of muscle mass and strength following cardiotoxin-induced injury were assessed. The muscle regeneration capacities under chronic hypoxia were compared between wildtype mice, MuSC-specific HIF-2α knockout mice, and mice treated with HIF-2α inhibitor PT2385, and angiotensin converting enzyme (ACE) inhibitor lisinopril. Transcriptomic analysis was performed to identify hypoxia- and HIF-2α-dependent molecular mechanisms. Statistical significance was determined using analysis of variance (ANOVA) and Mann-Whitney U tests. RESULTS: Chronic hypoxia led to limb muscle atrophy (EDL: 17.7%, P < 0.001; Soleus: 11.5% reduction in weight, P < 0.001) and weakness (10.0% reduction in peak-isometric torque, P < 0.001), along with impaired muscle regeneration characterized by diminished myofibre cross-sectional areas, increased fibrosis (P < 0.001), and incomplete strength recovery (92.3% of pre-injury levels, P < 0.05). HIF-2α stabilization in MuSC under chronic hypoxia hindered MuSC proliferation (26.1% reduction of MuSC at 10 dpi, P < 0.01). HIF-2α ablation in MuSC mitigated the adverse effects of chronic hypoxia on muscle regeneration and MuSC proliferation (30.9% increase in MuSC numbers at 10 dpi, P < 0.01), while HIF-1α ablation did not have the same effect. HIF-2α stabilization under chronic hypoxia led to elevated local ACE, a novel direct target of HIF-2α. Notably, pharmacological interventions with PT2385 or lisinopril enhanced muscle regeneration under chronic hypoxia (PT2385: 81.3% increase, P < 0.001; lisinopril: 34.6% increase in MuSC numbers at 10 dpi, P < 0.05), suggesting their therapeutic potential for alleviating chronic hypoxia-associated muscle atrophy. CONCLUSIONS: Chronic hypoxia detrimentally affects skeletal muscle regeneration by stabilizing HIF-2α in MuSC and thereby diminishing MuSC proliferation. HIF-2α increases local ACE levels in skeletal muscle, contributing to hypoxia-induced regenerative deficits. Administration of HIF-2α or ACE inhibitors may prove beneficial to ameliorate chronic hypoxia-associated muscle atrophy and weakness by improving muscle regeneration under chronic hypoxia.

ADP-Hep-Induced Liquid Phase Condensation of TIFA-TRAF6 Activates ALPK1/TIFA-Dependent Innate Immune Responses.

The ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with fork head-associated domain)-TRAF6 signaling pathway plays a pivotal role in regulating inflammatory processes, with TIFA and TRAF6 serving as key molecules in this cascade. Despite its significance, the functional mechanism of TIFA-TRAF6 remains incompletely understood. In this study, we unveil that TIFA undergoes liquid-liquid phase separation (LLPS) induced by ALPK1 in response to adenosine diphosphate (ADP)-ß-D-manno-heptose (ADP-Hep) recognition. The phase separation of TIFA is primarily driven by ALPK1, the pT9-FHA domain, and the intrinsically disordered region segment. Simultaneously, TRAF6 exhibits phase separation during ADP-Hep-induced inflammation, a phenomenon observed consistently across various inflammatory signal pathways. Moreover, TRAF6 is recruited within the TIFA condensates, facilitating lysine (K) 63-linked polyubiquitin chain synthesis. The subsequent recruitment, enrichment, and activation of downstream effectors within these condensates contribute to robust inflammatory signal transduction. Utilizing a novel chemical probe (compound 22), our analysis demonstrates that the activation of the ALPK1-TIFA-TRAF6 signaling pathway in response to small molecules necessitates the phase separation of TIFA. In summary, our findings reveal TIFA as a sensor for upstream signals, initiating the LLPS of itself and downstream proteins. This process results in the formation of membraneless condensates within the ALPK1-TIFA-TRAF6 pathway, suggesting potential applications in therapeutic biotechnology development.

Higher risk of hepatotoxicity associated with cabozantinib in cancer patients.

BACKGROUND: The efficacy of cabozantinib has attracted interest in various solid tumors. The primary aim of this study was to evaluate the risk of hepatotoxicity associated with cabozantinib in the patients with cancer. METHODS: PubMed, Cochrane, and EMBASE databases were searched for published randomized controlled trials (RCTs) from inception to September 9, 2023. The mainly outcomes were all-grade and grade ≥3 elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), expressed as relative risk (RR) and 95% confidence interval (CI). All data were pooled using fixed-effect or random-effects models according to the heterogeneity of the included RCTs. RESULTS: Among the 922 records identified, 8 RCTs incorporating 2613 patients with cancer were included. For patients receiving cabozantinib, the relative risks of all-grade AST elevation (RR, 2.63; 95% CI, 2.16-3.20, P < 0.001), all-grade ALT elevation (RR, 2.89; 95% CI, 2.31-3.60, P < 0.001), grade ≥3 AST elevation (RR, 2.26; 95% CI, 1.34-3.83, P = 0.002), and grade ≥3 ALT elevation (RR, 3.40; 95% CI, 1.65-7.01, P < 0.001) were higher than those of patients who did not receive cabozantinib group. Further subgroup analysis showed that the relative risk of hepatotoxicity associated with cabozantinib was higher than that in the other TKIs (erlotinib, sunitinib, and sorafenib) and the non-TKI drug groups (everolimus, prednisone, mitoxantrone, and paclitaxel). CONCLUSIONS: Compared with other solid tumor drugs, such as everolimus, sorafenib, sunitinib, paclitaxel, mitoxantrone-prednisone et al., cabozantinib has a higher risk of hepatotoxicity.

π-π Stacking Modulation via Polymer Adsorption for Elongated Exciton Diffusion in High-Efficiency Thick-Film Organic Solar Cells.

Developing efficient organic solar cells (OSCs) with thick active layers is crucial for roll-to-roll printing. However, thicker layers often result in lower efficiency. This study tackles this challenge using a polymer adsorption strategy combined with a layer-by-layer approach. Incorporating insulator polystyrene (PS) into the PM6:L8-BO system creates PM6+PS:L8-BO blends, effectively suppressing trap states and extending exciton diffusion length in the mixed donor domain. Adding insulating polymers with benzene rings to the donor enhances π-π stacking of donors, boosting intermolecular interactions and electron wave function overlap. This results in more orderly molecular stacking, longer exciton lifetimes, and higher diffusion lengths. The promoted long-range exciton diffusion leads to high power conversion efficiencies of 19.05% and 18.15% for PM6+PS:L8-BO blend films with 100 and 300 nm thickness, respectively, as well as a respectable 16.00% for 500 nm. These insights guide material selection for better exciton diffusion, and offer a method for thick-film OSC fabrication, promoting a prosperous future for practical OSC mass production.

Crossing the River by Feeling the Stones: Experiences with PD-1 Inhibitors in Geriatric Oncology People, a Case Report and Literature Review.

Currently, lung cancer remains one of the deadliest cancers, with a very high mortality rate, accounting for approximately 18% of all cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancer deaths. In particular, elderly patients generally have poor tolerance to chemotherapy or cannot tolerate chemotherapy. This case analysis focuses on an elderly patient with non-small cell lung cancer stage IV. The patient was an 86-year-old female with poor nutritional status and low body weight (27 kg) and could not tolerate platinum-based dual-drug first-line chemotherapy. This patient had tumour cells in alveolar lavage fluid without conditions examined for pd-l1 expression. However, the efficacy of previous first-line immunotherapy was positive, and the patient and his family members agreed to apply it, so there was no contraindication to apply anlotinib + pembrolizumab. Results were reviewed after two cycles, and CR was used to evaluate the efficacy. After four cycles, the efficacy was evaluated as complete remission (CR), the patient developed immune-related side effects, immunotherapy was suspended, and maintenance therapy with anlotinib was used. The most recent review was in 2023-6-9, and PET/CT indicated that the patient had sustained CR. In general, this case provides support for the successful possibility of a treatment strategy for elderly patients with poor physical fitness who cannot tolerate platinum-based doublet chemotherapy and who have driver gene-negative squamous cell lung cancer (PS>0-1).

Redox Chemistries for Vacancy Modulation in Plasmonic Copper Phosphide Nanocrystals.

Copper phosphide (Cu3-xP) nanocrystals are promising materials for nanoplasmonics due to their substoichiometric composition, enabling the generation and stabilization of excess delocalized holes and leading to localized surface plasmon resonance (LSPR) absorption in the near-IR. We present three Cu-coupled redox chemistries that allow postsynthetic modulation of the delocalized hole concentrations and corresponding LSPR absorption in colloidal Cu3-xP nanocrystals. Changes in the structural, optical, and compositional properties are evaluated by powder X-ray diffraction, electronic absorption spectroscopy, 31P magic-angle spinning solid-state nuclear magnetic resonance spectroscopy, and elemental analysis. The redox chemistries presented herein can be used to access nanocrystals with LSPR energies of 660-890 meV, a larger range than has been possible through synthetic tuning alone. In addition to utilizing previously reported redox chemistries used for copper chalcogenide nanocrystals, we show that the largest structural and LSPR modulation is achieved using a divalent metal halide and trioctylphosphine. Specifically, nanocrystals treated with zinc iodide and trioctylphosphine have the smallest unit-cell volume (295.2 Å3) reported for P63cm Cu3-xP, indicating more Cu vacancies than have been previously observed. Overall, these redox chemistries present valuable insight into controlling the optical and structural properties of Cu3-xP.

Enhancing vehicular emissions monitoring: A GA-GRU-based soft sensors approach for HDDVs.

Vehicle emissions have a serious impact on urban air quality and public health, so environmental authorities around the world have introduced increasingly stringent emission regulations to reduce vehicle exhaust emissions. Nowadays, PEMS (Portable Emission Measurement System) is the most widely used method to measure on-road NOx (Nitrogen Oxides) and PN (Particle Number) emissions from HDDVs (Heavy-Duty Diesel Vehicles). However, the use of PEMS requires a lot of workforce and resources, making it both costly and time-consuming. This study proposes a neural network based on a combination of GA (Genetic Algorithm) and GRU (Gated Recurrent Unit), which uses CC (Pearson Correlation Coefficient) to determine and simplify OBD (On-board Diagnosis) data. The GA-GRU model is trained under three real driving conditions of HDDVs, divided by vehicle driving parameters, and then embedded as a soft sensor in the OBD system to monitor real-time emissions of NOx and PN within the OBD system. This research addresses the existing research gap in the development of soft sensors specifically designed for NOx and PN emission monitoring. In this study, it is demonstrated that the described soft sensor has excellent R2 values and outperforms other conventional models. This research highlights the ability of the proposed soft sensor to eliminate outliers accurately and promptly while consistently tracking predictions throughout the vehicle's lifetime. This method is a groundbreaking update to the vehicle's OBD system, permanently adding monitoring data to the vehicle's OBD, thus fundamentally improving the vehicle's self-monitoring capabilities.

A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice.

Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.

Laparoscopic orchidopexy for the treatment of cryptorchidism in adults: a description of the technique and outcomes.

BACKGROUND: There are few studies on cryptorchidism in adults, and its treatment is still controversial. METHODS: To summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed. RESULTS: All testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach's triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery. CONCLUSION: Our study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient's reproductive hormone secretion function.