The immunologic role of IL-23 in psoriatic arthritis: a potential therapeutic target.

INTRODUCTION: Psoriatic arthritis (PsA) is a debilitating chronic condition characterized by inflammation of the joints, bones, enthesis, and skin. The pivotal role of interleukin-23 (IL-23) in the pathogenesis of PsA has become increasingly evident. This proinflammatory cytokine is markedly elevated in patients with PsA, suggesting its potential as a therapeutic target. Consequently, IL-23 inhibitors have emerged as promising first-line biologic treatments for PsA. AREAS COVERED: This review delves into the immunopathogenic mechanisms of IL-23 at the cellular and molecular levels in PsA. Furthermore, it provides the recent efficacy and safety profiles of IL-23 inhibitors. We conducted a literature search in PubMed for the following terms: 'IL-23 and psoriatic arthritis,' 'Ustekinumab,' 'Guselkumab,' 'Risankizumab,' and 'Tildrakizumab.' In addition, we retrieved clinical trials involving IL-23 inhibitors registered in ClinicalTrials.gov, EudraCT, and ICTRP. EXPERT OPINION: Despite the promising outcomes observed with IL-23 inhibitors, several challenges persist. The long-term effects of these agents require further investigation through prospective studies, and their limited accessibility worldwide necessitates urgent attention. Additionally, ongoing research is warranted to explore other potential drug targets within the IL-23/IL-23 R axis. The development of reliable biomarkers could greatly enhance early detection, tailored management strategies, and personalized treatment approaches for patients with PsA.

Achilles' spear: A new therapeutic target for age-related diseases.

The role of the senescence-associated secretory phenotype (SASP) in the development of age-related diseases is significant, and its control promises to have a tremendous positive impact on health. A recent study has identified a new mechanism for SASP regulation, titled miMOMP. Failure to regulate SASP would dramatically increase the risk of various age-related health problems. Nonetheless, we have not completely comprehended how to modulate SASP. In this commentary, we summarise the specific mechanisms by which miMOMP regulates SASP and outline possible future research directions. Moreover, potential risks and obstacles to the clinical translation of miMOMP are also presented.

Dynamic Changes in Qidan Aroma during Roasting: Characterization of Aroma Compounds and Their Kinetic Fitting.

Qidan is one of the most famous varieties of Wuyi Rock tea and has a strong aroma. The aroma-active compounds in Qidan subject to different roasting times were analyzed using solid-phase microextraction two-dimensional gas chromatography-olfactometry-mass spectrometry (SPME-GC×GC-O-MS), and a total of 92 aroma-active compounds were detected. Multivariate statistical analysis showed that the roasting time had a significant effect on the aroma characteristics of Qidan, and that the key products in the Maillard reaction accumulated with the extension of the roasting time; these key products were screened out according to the calculation of the odor activity values (OAVs), from which kinetic equations were established. It was found that the levels of 2-methylbutanal, 3-methylbutanal, 2-methylpyrazine, 2-ethyl-5-methylpyrazine, and benzaldehyde increased with time, while the contents of benzeneacetaldehyde showed a tendency to first increase and then decrease. This study provides a theoretical basis for flavor quality control during Qidan processing.

Rational Design of a Surface Acoustic Wave Device for Wearable Body Temperature Monitoring.

Continuous monitoring of vital signs based on advanced sensing technologies has attracted extensive attention due to the ravages of COVID-19. A maintenance-free and low-cost passive wireless sensing system based on surface acoustic wave (SAW) device can be used to continuously monitor temperature. However, the current SAW-based passive sensing system is mostly designed at a low frequency around 433 MHz, which leads to the relatively large size of SAW devices and antenna, hindering their application in wearable devices. In this paper, SAW devices with a resonant frequency distributed in the 870 MHz to 960 MHz range are rationally designed and fabricated. Based on the finite-element method (FEM) and coupling-of-modes (COM) model, the device parameters, including interdigital transducer (IDT) pairs, aperture size, and reflector pairs, are systematically optimized, and the theoretical and experimental results show high consistency. Finally, SAW temperature sensors with a quality factor greater than 2200 are obtained for real-time temperature monitoring ranging from 20 to 50 °C. Benefitting from the higher operating frequency, the size of the sensing system can be reduced for human body temperature monitoring, showing its potential to be used as a wearable monitoring device in the future.

Achilles' heel of male infertility: good LEGO players.

In a recent journal article, Chen et al. identified a germ cell-specific cofactor, STYXL1, associated with male fertility function. Deletion of STYXL1 prevents the LEGO player CCT complex from properly folding key microtubule proteins of the sperm flagellum, which affects sperm motility and male fertility function.

gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity.

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one ß-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 ß-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many ß-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.

Therapeutic strategies and predictive models for Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma in adults based on data of two Chinese medical centers.

OBJECTIVE: This study aims to establish an effective predictive model for predicting Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma (TFE3-RCC) and develop optimal therapeutic strategies. METHODS: Data from 4961 patients diagnosed with renal cell carcinoma at two medical centers in China were retrospectively analyzed. A cohort of 1571 patients from Zhejiang Provincial People's Hospital (Ra cohort) was selected to construct the model. Another cohort of 1124 patients from the Second Affiliated Hospital of Zhejiang Chinese Medical University was used for external validation (the Ha cohort). All patients with TFE3-RCC in both cohorts were included in the Ta cohort for the prognostic analysis. Univariate and multivariate binary logistic regression analyses were performed to identify independent predictors of the predictive nomogram. The apparent performance of the model was validated. Decision curve analysis was also performed to assess the clinical utility of the developed model. Factors associated with progression and prognosis in the Ta cohort were analyzed using the log-rank method, and Cox regression analysis and Kaplan-Meier survival curves were used to describe the effects of factors on prognosis and progression. RESULTS: Univariate and multivariate logistic regression analyses demonstrated that age, sex, BMI, smoking, eosinophils, and LDL were independent predictors of TFE3-RCC. Therefore, a predictive nomogram for TFE3-RCC, which had good discriminatory power (AUC = 0.796), was constructed. External validation (AUC = 0.806) also revealed good predictive ability. The calibration curves displayed good consistency between the predicted and observed incidences of TFE3-RCC. Invasion of regional lymph nodes, tyrosine kinase inhibitors, and surgical methods were independent factors associated with progression. Tyrosine kinase inhibitors are independent prognostic factors. CONCLUSION: This study not only proposed a high-precision clinical prediction model composed of various variables for the early diagnosis of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma but also optimized therapeutic strategies through prognostic analysis.

One new species of the genus Capnogryllacris Karny, 1937 (Orthoptera: Gryllacrididae) from China.

The paper reports a new species of the genus Capnogryllacris Karny, 1937 (Orthoptera: Gryllacrididae) from China, i.e. Capnogryllacris latilamargis sp. nov. The all specimens are deposited in the Museum of Hebei University, Baoding, China.

Two new species of the genus Ocellarnaca Gorochov, 2004 (Orthoptera: Gryllacrididae) from China.

The paper reports two new species of the genus Ocellarnaca Gorochov, 2004 (Orthoptera: Gryllacrididae) from China, i.e. Ocellarnaca longiprotubera sp. nov. and Ocellarnaca grossa sp. nov. The type specimens are deposited in the Museum of Hebei University, Baoding 071002, China.

Defect-Rich Single Atom Catalyst Enhanced Polysulfide Conversion Kinetics to Upgrade Performance of Li-S Batteries.

Lithium-sulfur (Li-S) batteries have attracted considerable attention owing to their extremely high energy densities. However, the application of Li-S batteries has been limited by low sulfur utilization, poor cycle stability, and low rate capability. Accelerating the rapid transformation of polysulfides is an effective approach for addressing these obstacles. In this study, a defect-rich single-atom catalytic material (Fe-N4/DCS) is designed. The abundantly defective environment is favorable for the uniform dispersion and stable existence of single-atom Fe, which not only improves the utilization of single-atom Fe but also efficiently adsorbs polysulfides and catalyzes the rapid transformation of polysulfides. To fully exploit the catalytic activity, catalytic materials are used to modify the routine separator (Fe-N4 /DCS/PP). Density functional theory and in situ Raman spectroscopy are used to demonstrate that Fe-N4 /DCS can effectively inhibit the shuttling of polysulfides and accelerate the redox reaction. Consequently, the Li-S battery with the modified separator achieves an ultralong cycle life (a capacity decay rate of only 0.03% per cycle at a current of 2 C after 800 cycles), and an excellent rate capability (894 mAh g-1 at 3 C). Even at a high sulfur loading of 5.51 mg cm-2 at 0.2 C, the reversible areal capacity still reaches 5.4 mAh cm-2 .

Trilobatin, an Active Dihydrochalcone from Lithocarpus polystachyus, Prevents Cisplatin-Induced Nephrotoxicity via Mitogen-Activated Protein Kinase Pathway-Mediated Apoptosis in Mice.

Although naturally occurring flavonoids have shown beneficial effects on the side effects caused by cisplatin, there are few reports on the protective effect of dihydrochalcone on the cisplatin-induced toxicity. Trilobatin (TLB), as the major sweetener and active ingredient in Lithocarpus polystachyus Rehd, is a dihydrochalcone-like compound that can be present in concentrations of up to 10% or more in tender leaves. Herein, a cisplatin-induced acute kidney injury (AKI) model was established to investigate the protective effect and mechanism of TLB against the cisplatin-induced nephrotoxicity in mice. The results showed that TLB significantly reversed the inhibition of CRE, BUN, and MDA levels compared with the cisplatin group. Furthermore, TLB treatment (50 and 100 mg/kg) for 10 days significantly alleviated cisplatin-induced renal pathological changes. TUNEL staining showed that TLB administration can effectively improve the occurrence of apoptosis of renal tissue cells caused by cisplatin exposure. Importantly, western blot analysis verified that TLB alleviated cisplatin-induced nephrotoxicity by regulating the AKT/MAPK signaling pathway and apoptosis. In summary, our findings showed clearly that TLB has a significant preventive effect on cisplatin-induced AKI.

Response mechanism of Chlamydomonas reinhardtii to nanoscale bismuth oxyiodide (nano-BiOI): Integrating analysis of mineral nutrient metabolism and metabolomics.

Nanoscale bismuth oxyiodide (nano-BiOI) is widely studied and applied in environmental applications and biomedical fields, with the consequence that it may be deposited into aquatic environments. However, the impact of nano-BiOI on aquatic ecosystems, especially freshwater microalga, remains limited. Herein, the nano-BiOI was synthesized and its response mechanism towards microalga Chlamydomonas reinhardtii was evaluated. Results showed that a low concentration of nano-BiOI (5 mg/L) could stimulate algal growth at the early stage of stress. With the increase in concentration, the growth rate of algal cells was inhibited and showed a dose effect. Intracellular reactive oxygen species (ROS) were significantly induced and accompanied by enhanced lipid peroxidation, decreased nonspecific esterase activity, and significantly upregulated glutathione S-transferase activity (GST) activity. Mineral nutrient metabolism analysis showed that nano-BiOI significantly interfered with the mineral nutrients of the algae. Non-targeted metabolomics identified 35 different metabolites (DEMs, 22 upregulated, and 13 downregulated) under 100 mg/L BiOI stress. Metabolic pathway analysis demonstrated that a high concentration of nano-BiOI significantly induced metabolic pathways related to amino acid biosynthesis, lipid biosynthesis, and glutathione biosynthesis, and significantly inhibited the sterol biosynthesis pathway. This finding will contribute to understanding the toxicological mechanisms of nano-BiOI on C. reinhardtii.

Clinical effect of micturition interruption exercise on urinary incontinence after radical prostatectomy.

PURPOSE: To explore the effectiveness of micturition interruption exercise in improving the incidence of urinary incontinence after radical prostatectomy. MATERIALS AND METHODS: With a retrospective case-control study, 96 patients admitted in the Second Affiliated Hospital of Zhejiang Chinese Medical University from August 2014 to August 2020 and underwent radical prostatectomy were collected as the subjects. Those patients who used micturition interruption exercise (n = 48) were set as the therapy group, and the control group was collected according to the ratio of 1:1; the patients used Kegel exercise (n = 48) to compare the rehabilitation of urinary incontinence in patients and the effect of training compliance on rehabilitation. RESULTS: The recovery time of urinary incontinence in the therapy group was significantly shorter than that of the control group. In the therapy group, 83.3% of patients with training compliance reached an average or above, while the control group only accounted for 58.3%. International Consultation on Incontinence Questionnaire Short-Form score of the therapy group was lower than that of the control group after surgery. Spearman analysis suggests that there is a negative correlation between the postoperative urinary incontinence recovery time and compliance with the micturition interruption exercise. CONCLUSIONS: Micturition interruption exercise could not only improve the compliance of patients with exercise, but also significantly shorten the recovery time of urinary incontinence after radical prostatectomy.

MutexMatch: Semi-Supervised Learning With Mutex-Based Consistency Regularization.

The core issue in semi-supervised learning (SSL) lies in how to effectively leverage unlabeled data, whereas most existing methods tend to put a great emphasis on the utilization of high-confidence samples yet seldom fully explore the usage of low-confidence samples. In this article, we aim to utilize low-confidence samples in a novel way with our proposed mutex-based consistency regularization, namely MutexMatch. Specifically, the high-confidence samples are required to exactly predict "what it is" by the conventional true-positive classifier (TPC), while low-confidence samples are employed to achieve a simpler goal-to predict with ease "what it is not" by the true-negative classifier (TNC). In this sense, we not only mitigate the pseudo-labeling errors but also make full use of the low-confidence unlabeled data by the consistency of dissimilarity degree. MutexMatch achieves superior performance on multiple benchmark datasets, i.e., Canadian Institute for Advanced Research (CIFAR)-10, CIFAR-100, street view house numbers (SVHN), self-taught learning 10 (STL-10), and mini-ImageNet. More importantly, our method further shows superiority when the amount of labeled data is scarce, e.g., 92.23% accuracy with only 20 labeled data on CIFAR-10. Code has been released at https://github.com/NJUyued/MutexMatch4SSL.

Cascade Reaction of 2-Naphthols and Azirines: One-Pot Synthesis of C-3 Naphthol-Substituted Benzo[e]indoles.

A copper-catalyzed annulation of 3-aryl-2H-azirines with 2-naphthols has been developed for the rapid assembly of C-3-naphthol-substituted benzo[e]indoles in one pot. This cascade reaction was realized through dearomatic nucleophilic ring opening of azirine, intramolecular cyclization, and oxidative cross-dehydrogenative coupling to furnish the important unreported π-expanded naphthol/benzo[e]indole biaryls.

Nano-herb medicine and PDT induced synergistic immunotherapy for colon cancer treatment.

A variety of therapies have been developed and used for the treatment of colon cancer, however, the high mortality rate remains high and more effective strategies are still in urgent needs. In this study, an immunotherapy approach that is composed of innate immune activator Astragaloside III (As) and the photodynamic therapy (PDT) reagent chlorine e6 (Ce6) ((As + Ce6)@MSNs-PEG), was developed for colon cancer treatment. We showed that (As + Ce6)@MSNs-PEG could effectively activate NK cells and inhibit the proliferation of tumor cells in vitro. It could also effectively reach tumor sites, induce infiltration of immune cells into the tumor, and enhance the cytotoxicity of natural killer cells and CD8+ T cells in vivo. Without obvious side effects, (As + Ce6)@MSNs-PEG treatment significantly inhibited tumor growth and extended the lifespan of tumor-bearing mice. Further results revealed that treatment of (As + Ce6)@MSNs-PEG led to enhanced IFN secretion by immune cells and increased T-box transcription factor (T-bet), which is highly expressed by T cells. Therefore, (As + Ce6)@MSNs-PEG may serve as an effective and safe platform for combinatory use with nano-herb medicine and PDT to provide a new therapy for colon cancer treatment.

Immune Modulator and Low-Temperature PTT-Induced Synergistic Immunotherapy for Cancer Treatment.

Immunotherapy has shown great potential in cancer therapeutics but has limitations of the insufficient activation of dendritic cells (DCs) and immune-suppressive microenvironment. To overcome these obstacles, a cascade synergistic immunotherapy nanosystem (denoted as CpG@PDA-FA) was designed to elevate anticancer immune response. The combination nanosystem including a photothermal agent polydopamine (PDA) and immunomodulator CpG oligodeoxynucleotides (CpG ODNs). On the one hand, polydopamine (PDA) acts as a photothermal agent to induce low-temperature PTT. It leads to immunogenic cell death (ICD), a programmed cell death pathway, which can activate DCs and enhance the antitumor immune response of T cells. On the other hand, CpG ODNs further promote maturation and migration of DCs as well as ameliorates the immunosuppression microenvironment of the tumor (TME). This paper focuses on a cancer synergistic treatment of ICD-induced immunotherapy by low-temperature PTT and ameliorates TME by immunomodulator CpG ODNs. We proved that CpG@PDA-FA NPs realized a remarkable synergistic treatment effect compared with respective single PTT or CpG therapy in the maturation of DCs and activation of T cells. In addition, CpG@PDA-FA NPs also reduced myeloid-derived suppressor cells and regulatory T cells to relieve immunosuppression. Hence, CpG@PDA-FA NPs provide a bidirectional immunotherapy strategy for tumor inhibition and highlight the cascade effects of low-temperature PTT and immunotherapy.

Medical image segmentation and reconstruction of prostate tumor based on 3D AlexNet.

BACKGROUND: Prostate cancer is a disease with a high incidence of tumors in men. Due to the long incubation time and insidious condition, early diagnosis is difficult; especially imaging diagnosis is more difficult. In actual clinical practice, the method of manual segmentation by medical experts is mainly used, which is time-consuming and labor-intensive and relies heavily on the experience and ability of medical experts. The rapid, accurate and repeatable segmentation of the prostate area is still a challenging problem. It is important to explore the automated segmentation of prostate images based on the 3D AlexNet network. METHOD: Taking the medical image of prostate cancer as the entry point, the three-dimensional data is introduced into the deep learning convolutional neural network. This paper proposes a 3D AlexNet method for the automatic segmentation of prostate cancer magnetic resonance images, and the general network ResNet 50, Inception -V4 compares network performance. RESULTS: Based on the training samples of magnetic resonance images of 500 prostate cancer patients, a set of 3D AlexNet with simple structure and excellent performance was established through adaptive improvement on the basis of classic AlexNet. The accuracy rate was as high as 0.921, the specificity was 0.896, and the sensitivity It is 0.902 and the area under the receiver operating characteristic curve (AUC) is 0.964. The Mean Absolute Distance (MAD) between the segmentation result and the medical expert's gold standard is 0.356 mm, and the Hausdorff distance (HD) is 1.024 mm, the Dice similarity coefficient is 0.9768. CONCLUSION: The improved 3D AlexNet can automatically complete the structured segmentation of prostate magnetic resonance images. Compared with traditional segmentation methods and depth segmentation methods, the performance of the 3D AlexNet network is superior in terms of training time and parameter amount, or network performance evaluation. Compared with the algorithm, it proves the effectiveness of this method.

[Prostatic fibrosis: Progress in studies].

The prostate volume is not enlarged in some patients with lower urinary tract symptoms (LUTS). Evidence shows that prostate fibrosis, in addition to BPH and smooth muscle dysfunction, is one of the causes of LUTS, and that its occurrence is related to inflammation of various causes, ischemia, hypoxia and drugs, with the differentiation, aggregation and activation of myofibroblasts involved in its pathogenesis. Therefore, anti-inflammation and anti-fibrosis strategies may be considered as potential targets for the treatment of LUTS. This article presents an overview on the causes of prostatic fibrosis, its diagnosis, its association with LUTS, and the advances in its treatment.

A Novel Targeted and High-Efficiency Nanosystem for Combinational Therapy for Alzheimer's Disease.

Alzheimer's disease (AD) remains the most prevalent neurodegenerative disease, and no effective treatment is available yet. Metal-ion-triggered aggregates of amyloid-beta (Aß) peptide and acetylcholine imbalance are reported to be possible factors in AD pathogenesis. Thus, a combination therapy that can not only inhibit and reduce Aß aggregation but also simultaneously regulate acetylcholine imbalance that can serve as a potential treatment for AD is needed. Here, clioquinol (metal-ion chelating agent) and donepezil (acetylcholinesterase (AChE) inhibitor) co-encapsulated human serum albumin (HSA) nanoparticles (dcHGT NPs) are designed, which are modified with transcriptional activator protein (TAT) and monosialotetrahexosylganglioside (GM1). The GM1 lipid and TAT peptide endow this drug delivery nanosystem with high brain entry efficiency and long-term retention capabilities through intranasal administration. It is found that dcHGT NPs can significantly inhibit and eliminate Aß aggregation, relieve acetylcholine-related inflammation in microglial cells, and protect primary neurons from Aß oligomer-induced neurotoxicity in vitro. The alleviation of Aß-related inflammation and AChE-inhibited effect further synergistically adjust acetylcholine imbalance. It is further demonstrated that dcHGT NPs reduce Aß deposition, ameliorate neuron morphological changes, rescue memory deficits, and greatly improve acetylcholine regulation ability in vivo. This multifunctional synergetic nanosystem can be a new candidate to achieve highly efficient combination therapy for AD.