Automatic Quality Assessment of Pork Belly via Deep Learning and Ultrasound Imaging.

Pork belly, prized for its unique flavor and texture, is often overlooked in breeding programs that prioritize lean meat production. The quality of pork belly is determined by the number and distribution of muscle and fat layers. This study aimed to assess the number of pork belly layers using deep learning techniques. Initially, semantic segmentation was considered, but the intersection over union (IoU) scores for the segmented parts were below 70%, which is insufficient for practical application. Consequently, the focus shifted to image classification methods. Based on the number of fat and muscle layers, a dataset was categorized into three groups: three layers (n = 1811), five layers (n = 1294), and seven layers (n = 879). Drawing upon established model architectures, the initial model was refined for the task of learning and predicting layer traits from B-ultrasound images of pork belly. After a thorough evaluation of various performance metrics, the ResNet18 model emerged as the most effective, achieving a remarkable training set accuracy of 99.99% and a validation set accuracy of 96.22%, with corresponding loss values of 0.1478 and 0.1976. The robustness of the model was confirmed through three interpretable analysis methods, including grad-CAM, ensuring its reliability. Furthermore, the model was successfully deployed in a local setting to process B-ultrasound video frames in real time, consistently identifying the pork belly layer count with a confidence level exceeding 70%. By employing a scoring system with 100 points as the threshold, the number of pork belly layers in vivo was categorized into superior and inferior grades. This innovative system offers immediate decision-making support for breeding determinations and presents a highly efficient and precise method for assessment of pork belly layers.

A Time-Dependent Damage Constitutive Model for Brittle Rock Materials Based on Subcritical Damage Theory.

In the domain of geotechnical engineering, a profound understanding of the long-term mechanical deformation characteristics of rocks is indispensable for the design and construction of structures, dams, tunnels, and various engineering projects. The deformation behavior of rocks under long-term loads directly impacts the stability and safety of engineering structures. This study employs micromechanical methods to investigate the subcritical extension of microcracks under stress corrosion. By examining the accumulated damage resulting from this phenomenon, the research explores the patterns of aging damage development and establishes a constitutive model for aging that incorporates cumulative damage over the stress history. The accuracy of the proposed model is evaluated through a comprehensive comparison of numerical results with experimental data. The experimental data set encompasses traditional triaxial compression tests, single-stage creep, multistage creep, and single-stage relaxation tests conducted under varying confining pressures. The predicted results exhibit strong consistency with the entire data set. Furthermore, this paper employs crack damage stress as an indicator characterizing the long-term strength of rock. Through frictional damage coupling analysis and derivation, an analytical expression for the long-term strength of rock materials containing microcracks is provided, serving as a theoretical basis for investigating the long-term mechanical performance of brittle rock materials and ensuring the long-term stability of large-scale rock engineering projects.

Transformation of spatial representations along hippocampal circuits.

The hippocampus is thought to provide the brain with a cognitive map of the external world by processing various types of spatial information. To understand how essential spatial variables such as direction, position, and distance are transformed along its circuits to construct this global map, we perform single-photon widefield microendoscope calcium imaging in the dentate gyrus and CA3 of mice freely navigating along a narrow corridor. We find that spatial activity maps in the dentate gyrus, but not in CA3, are correlated after aligning them to the running directions, suggesting that they represent the distance traveled along the track in egocentric coordinates. Together with population activity decoding, our data suggest that while spatial representations in the dentate gyrus and CA3 are anchored in both egocentric and allocentric coordinates, egocentric distance coding is more prevalent in the dentate gyrus than in CA3, providing insights into the assembly of the cognitive map.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

Improved Proton Conductivity of Chitosan-Based Composite Proton Exchange Membrane Reinforced by Modified GO Inorganic Nanofillers.

Non-fluorinated chitosan-based proton exchange membranes (PEMs) have been attracting considerable interest due to their environmental friendliness and relatively low cost. However, low proton conductivity and poor physicochemical properties have limited their application in fuel cells. In this work, a reinforced nanofiller (sulfonated CS/GO, S-CS/GO) is accomplished, for the first time, via a facile amidation and sulfonation reaction. Novel chitosan-based composite PEMs are successfully constructed by the incorporation of the nanofiller into the chitosan matrix. Additionally, the effects of the type and amount of the nanofillers on physicochemical and electrochemical properties are further investigated. It is demonstrated that the chitosan-based composite PEMs incorporating an appropriate amount of the nanofillers (9 wt.%) exhibit good membrane-forming ability, physicochemical properties, improved proton conductivity, and low methanol permeability even under a high temperature and low humidity environment. When the incorporated amounts of S-CS/GO are 9 wt.%, the proton conductivity of the composite PEMs was up to 0.032 S/cm but methanol permeability was decreased to 1.42 × 10-7 cm2/s. Compared to a pristine CS membrane, the tensile strength of the composite membrane is improved by 98% and the methanol permeability is reduced by 51%.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

The efficacy and safety of monoclonal antibody therapies for interstitial cystitis/bladder pain syndrome: A meta-analysis of randomized controlled trials.

OBJECTIVES: This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. RESULTS: Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. CONCLUSIONS: The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

The Function and Mechanism of Long Noncoding RNAs in Adipogenic Differentiation.

Adipocytes are crucial for maintaining energy balance. Adipocyte differentiation involves distinct stages, including the orientation stage, clone amplification stage, clone amplification termination stage, and terminal differentiation stage. Understanding the regulatory mechanisms governing adipogenic differentiation is essential for comprehending the physiological processes and identifying potential biomarkers and therapeutic targets for metabolic diseases, ultimately improving glucose and fat metabolism. Adipogenic differentiation is influenced not only by key factors such as hormones, the peroxisome proliferator-activated receptor (PPAR) family, and the CCATT enhancer-binding protein (C/EBP) family but also by noncoding RNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Among these, lncRNA has been identified as a significant regulator in adipogenic differentiation. Research has demonstrated various ways in which lncRNAs contribute to the molecular mechanisms of adipogenic differentiation. Throughout the adipogenesis process, lncRNAs modulate adipocyte differentiation and development by influencing relevant signaling pathways and transcription factors. This review provides a brief overview of the function and mechanism of lncRNAs in adipogenic differentiation.

Advancing Energy Sustainability Through Solar-to-Fuel Technologies: From Materials to Devices and Systems.

To achieve carbon neutrality and sustainable development, innovative solar-to-fuel systems have been designed through the integration of solar energy harvesting and electrochemical devices. Over the last decade, there have been notable advancements in enhancing the efficiency and durability of these solar-to-fuel systems. Despite the advancements, there remains significant potential for further improvements in the performance of systems. Enhancements can be achieved by optimizing electrochemical catalysts, advancing the manufacturing technologies of photovoltaics and electrochemical cells, and refining the overall design of these systems. In the realm of catalyst optimization, the effectiveness of materials can be significantly improved through active site engineering and strategic use of functional groups. Similarly, the performance of electrochemical devices can be enhanced by incorporating specific additives into electrolytes and optimizing gas diffusion electrodes. Improvements in solar harvesting devices are achievable through efficient passivant and self-assembled monolayers, which enhance the overall quality and efficiency of these systems. Additionally, optimizing the energy conversion efficiency involves the strategic use of DC converters, photoelectrodes, and redox media. This review aims to provide a comprehensive overview of the advancements in solar-powered electrochemical energy conversion systems, laying a solid foundation for future research and development in the field of energy sustainability.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

ALKBH5 regulates chicken adipogenesis by mediating LCAT mRNA stability depending on m6A modification.

BACKGROUND: Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. RESULTS: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. CONCLUSIONS: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.

Iridium(III) carbene complexes as potent girdin inhibitors against metastatic cancers.

Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative breast cancer xenograft tumors, impedes the metastatic spread of breast cancer cells, and can be modified into an antibody-drug conjugate payload to achieve precise tumor delivery in mice. Identified by thermal proteome profiling, an important molecular target of 1a in cellulo is Girdin, a multifunctional adaptor protein that is overexpressed in cancer cells and unequivocally serves as a signaling hub for multiple pivotal oncogenic pathways. However, specific small-molecule inhibitors of Girdin have not yet been developed. Notably, 1a exhibits high binding affinity to Girdin with a Kd of 1.3 µM and targets the Girdin-linked EGFR/AKT/mTOR/STAT3 cancer-driving pathway, inhibiting cancer cell proliferation and metastatic activity. Our study reveals a potent Girdin-targeting anticancer compound and demonstrates that octahedral metal complexes constitute an untapped library of small-molecule inhibitors that can fit into the ligand-binding pockets of key oncoproteins.

Immunomodulatory poly(L-lactic acid) nanofibrous membranes promote diabetic wound healing by inhibiting inflammation, oxidation and bacterial infection.

Background: Given the significant impact on human health, it is imperative to develop novel treatment approaches for diabetic wounds, which are prevalent and serious complications of diabetes. The diabetic wound microenvironment has a high level of reactive oxygen species (ROS) and an imbalance between proinflammatory and anti-inflammatory cells/factors, which hamper the healing of chronic wounds. This study aimed to develop poly(L-lactic acid) (PLLA) nanofibrous membranes incorporating curcumin and silver nanoparticles (AgNPs), defined as PLLA/C/Ag, for diabetic wound healing. Methods: PLLA/C/Ag were fabricated via an air-jet spinning approach. The membranes underwent preparation and characterization through various techniques including Fourier-transform infrared spectroscopy, measurement of water contact angle, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy, assessment of in vitro release of curcumin and Ag+, testing of mechanical strength, flexibility, water absorption and biodegradability. In addition, the antioxidant, antibacterial and anti-inflammatory properties of the membranes were evaluated in vitro, and the ability of the membranes to heal wounds was tested in vivo using diabetic mice. Results: Loose hydrophilic nanofibrous membranes with uniform fibre sizes were prepared through air-jet spinning. The membranes enabled the efficient and sustained release of curcumin. More importantly, antibacterial AgNPs were successfully reduced in situ from AgNO3. The incorporation of AgNPs endowed the membrane with superior antibacterial activity, and the bioactivities of curcumin and the AgNPs gave the membrane efficient ROS scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further results from animal studies indicated that the PLLA/C/Ag membranes had the most efficient wound healing properties, which were achieved by stimulating angiogenesis and collagen deposition and inhibiting inflammation. Conclusions: In this research, we successfully fabricated PLLA/C/Ag membranes that possess properties of antioxidants, antibacterial agents and anti-inflammatory agents, which can aid in the process of wound healing. Modulating wound inflammation, these new PLLA/C/Ag membranes serve as a novel dressing to enhance the healing of diabetic wounds.

Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation.

BACKGROUND: Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies. METHODS: SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation. RESULTS: The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4. CONCLUSION: In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways.

Highly Efficient and Scalable p-i-n Perovskite Solar Cells Enabled by Poly-metallocene Interfaces.

Inverted p-i-n perovskite solar cells (PSCs) are easy to process but need improved interface characteristics with reduced energy loss to prevent efficiency drops when increasing the active photovoltaic area. Here, we report a series of poly ferrocenyl molecules that can modulate the perovskite surface enabling the construction of small- and large-area PSCs. We found that the perovskite-ferrocenyl interaction forms a hybrid complex with enhanced surface coordination strength and activated electronic states, leading to lower interfacial nonradiative recombination and charge transport resistance losses. The resulting PSCs achieve an enhanced efficiency of up to 26.08% for small-area devices and 24.51% for large-area devices (1.0208 cm2). Moreover, the large-area PSCs maintain >92% of the initial efficiency after 2000 h of continuous operation at the maximum power point under 1-sun illumination and 65 °C.

Semaglutide alleviates early brain injury following subarachnoid hemorrhage by suppressing ferroptosis and neuroinflammation via SIRT1 pathway.

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a major cause of incapacity and death, imposing a significant economic burden globally. Additionally, SAH is the third most prevalent form of stroke. Semaglutide affects oxidative stress, inflammation, and mitochondrial biogenesis. Specifically, the potential neuroprotective effect of semaglutide in SAH and its underlying mechanism is unclear. Accordingly, the present research intended to explore the neuroprotective effect of semaglutide in SAH and its potential molecular mechanisms. METHODS: We constructed a C57BL/6 mouse model of SAH. The parameters assessed were neuronal ferroptosis, neuroinflammatory cytokine levels, reactive oxygen species (ROS) levels, glutathione (GSH) and malondialdehyde (MDA) levels, brain water content, and neurological score. RESULTS: The results showed that the activation of semaglutide significantly increased neurological scores, relieved cerebral edema, decreased the levels of inflammatory cytokine nuclear factor kappa B, interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, MDA, and ROS, and increased the levels of GSH. Suppression of SIRT1 reversed these effects, indicating that semaglutide activated SIRT1 to reduce neuroinflammation, ferroptosis, and neuronal cell death after SAH. Thus, the activation of the Nrf2/HO-1 signaling pathway contributes to the neuroprotective properties of semaglutide. CONCLUSIONS: Semaglutide can improve murine neurological outcomes and reduce neuronal damage against neuroinflammation and ferroptosis.

Case report and literature review of rezvilutamide in the treatment of hormone-sensitive prostate cancer.

Background: Prostate cancer represents a major health concern worldwide, with the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and locally advanced prostate cancer posing a particular challenge. Rezvilutamide, a new androgen receptor antagonist from China, has shown early promise; however, its real-world effectiveness and safety profile require further evidence. This case series evaluates the preliminary clinical outcomes of rezvilutamide in combination with androgen deprivation therapy (ADT), focusing on PSA response and radiological findings across various stages of prostate cancer in four patients. Case description: Case 1 details a 68-year-old male with low-volume mHSPC who exhibited a positive therapeutic response, demonstrated by decreasing PSA levels and improved radiographic results, despite experiencing mild side effects related to the drug. Case 2 describes a 71-year-old male with high-volume mHSPC who had a favorable outcome, with no significant changes in tumor size or metastatic spread and no negative reactions to the drug. Case 3 involves a 55-year-old male with locally advanced prostate cancer, who saw a reduction in PSA levels and a small decrease in tumor volume, yet with ongoing bladder involvement. Genetic testing showed no significant mutations. Case 4 presents a 74-year-old male with extensive metastatic disease who initially responded to the treatment but later exhibited disease advancement and an ATM gene mutation, signaling a shift to metastatic castration-resistant prostate cancer (mCRPC). This finding underscores the crucial role of genetic testing in directing future treatment, with therapies such as olaparib or chemotherapy being advised. Conclusions: Rezvilutamide has shown a potential benefit in the management of mHSPC and locally advanced prostate cancer, generally with a mild safety profile. Initial positive responses, particularly in PSA decline and radiographic progression, are promising. Nevertheless, the varying responses, notably concerning genetic mutations, highlight the necessity for tailored treatment approaches. Due to the small cohort and brief follow-up period, more extensive research with larger populations and prolonged monitoring is essential to conclusively determine the benefits and safety of rezvilutamide. The utilization of genetic insights is key to refining treatment decisions and enhancing outcomes for patients with advanced prostate cancer.

Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis.

BACKGROUND: Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. METHODS: Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 µmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. RESULTS AND DISCUSSION: Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. CONCLUSION: Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Effectiveness of Ixekizumab in Chinese Patients with Moderate-Severe Plaque Psoriasis with Special Area Involvement: Subanalysis of a Prospective, Multicenter, Observational Real-World Study.

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). METHODS: A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. RESULTS: In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. CONCLUSION: Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.