Ultrasound Induces Local Disorder of FeOOH on CdIn2S4 Photoanode for High Efficiency Photoelectrochemical Water Oxidation.

The regulation of the crystal structure of oxygen evolution cocatalyst (OEC) is a promising strategy for enhancing the photoelectrochemical efficiency of photoanodes. However, the prevailing regulating approach typically requires a multistep procedure, presenting a significant challenge for maintaining the structural integrity and performance of the photoanode. Herein, FeOOH with a local disordered structure is directly grown on a CdIn2S4 (CIS) photoanode via a simple and mild sonochemical approach. By modulating the localized supersaturation of Ni ions, ultrasonic cavitation induces Ni ions to participate in the nucleation and growth of FeOOH clusters to cause local disorder of FeOOH. Consequently, the local disordered FeOOH facilitates the exposure of additional active sites, boosting OER kinetics and extending charge carrier lifetimes. Finally, the optimal photoanode reaches 4.52 mA cm-2 at 1.23 VRHE, and the onset potential shifts negatively by 330 mV, exhibiting excellent performance compared with that of other metal sulfide-based photoelectrodes reported thus far. This work provides a mild and controllable sonochemical method for regulating the phase structure of OECs to construct high-performance photoanodes.

Inhibition of the RBMS1/PRNP axis improves ferroptosis resistance-mediated oxaliplatin chemoresistance in colorectal cancer.

The majority of patients with advanced colorectal cancer have chemoresistance to oxaliplatin, and studies on oxaliplatin resistance are limited. Our research showed that RNA-binding motif single-stranded interacting protein 1 (RBMS1) caused ferroptosis resistance in tumor cells, leading to oxaliplatin resistance. We employed bioinformatics to evaluate publically accessible data sets and discovered that RBMS1 was significantly upregulated in oxaliplatin-resistant colorectal cancer cells, in tandem with ferroptosis suppression. In vivo and in vitro studies revealed that inhibiting RBMS1 expression caused ferroptosis in colorectal cancer cells, restoring tumor cell sensitivity to oxaliplatin. Mechanistically, this is due to RBMS1 inducing prion protein translation, resulting in ferroptosis resistance in tumor cells. Validation of clinical specimens revealed that RBMS1 is similarly linked to tumor development and a poor prognosis. Overall, RBMS1 is a potential therapeutic target with clinical translational potential, particularly for oxaliplatin chemoresistance in colorectal cancer.

Recombinant human IL-37 attenuates acute cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.

Interleukin-37 contributes to endometrial regenerative cell-mediated immunotherapeutic effect on chronic allograft vasculopathy.

BACKGROUND AIMS: Chronic allograft vasculopathy (CAV) remains a predominant contributor to late allograft failure after organ transplantation. Several factors have already been shown to facilitate the progression of CAV, and there is still an urgent need for effective and specific therapeutic approaches to inhibit CAV. Human mesenchymal-like endometrial regenerative cells (ERCs) are free from the deficiencies of traditional invasive acquisition methods and possess many advantages. Nevertheless, the exact immunomodulation mechanism of ERCs remains to be elucidated. METHODS: C57BL/6 (B6) mouse recipients receiving BALB/c mouse donor abdominal aorta transplantation were treated with ERCs, negative control (NC)-ERCs and interleukin (IL)-37-/-ERCs (ERCs with IL-37 ablation), respectively. Pathologic lesions and inflammatory cell infiltration in the grafts, splenic immune cell populations, circulating donor-specific antibody levels and cytokine profiles were analyzed on postoperative day (POD) 40. The proliferative capacities of Th1, Th17 and Treg subpopulations were assessed in vitro. RESULTS: Allografts from untreated recipients developed typical pathology features of CAV, namely endothelial thickening, on POD 40. Compared with untreated and IL-37-/-ERC-treated groups, IL-37-secreting ERCs (ERCs and NC-ERCs) significantly reduced vascular stenosis, the intimal hyperplasia and collagen deposition. IL-37-secreting ERCs significantly inhibited the proliferation of CD4+T cells, reduced the proportions of Th1 and Th17 cells, but increased the proportion of Tregs in vitro. Furthermore, in vitro results also showed that IL-37-secreting ERCs significantly inhibited Th1 and Th17 cell responses, abolished B-cell activation, diminished donor-specific antibody production and increased Treg proportions. Notably, IL-37-secreting ERCs remarkably downregulated the levels of pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, IL-1ß, IL-6 and IL-17A) and increased IL-10 levels in transplant recipients. CONCLUSIONS: The knockdown of IL-37 dramatically abrogates the therapeutic ability of ERCs for CAV. Thus, this study highlights that IL-37 is indispensable for ERC-mediated immunomodulation for CAV and improves the long-term allograft acceptance.

Equibiaxial strain regulates the electronic structure and mechanical, piezoelectric, and thermal transport properties of the 2H-phase monolayers CrX2 (X = S, Se, Te).

A superior piezoelectric coefficient and diminutive lattice thermal conductivity are advantageous for the application of a two-dimensional semiconductor in piezoelectric and thermoelectric devices, whereas an imperfect piezoelectric coefficient and large lattice thermal conductivity limit the practical application of the material. In this study, we investigate how the equibiaxial strain regulates the electronic structure, and mechanical, piezoelectric, and thermal transport properties. Tensile strain can deduce the bandgap of the monolayer CrX2 (X = S, Se, Te), whereas compressive strain has an opposite effect. Additionally, the transition from a semiconductor to a metal state and the transition between direct and indirect band gaps will occur at appropriate strain values, so the electronic structure can be effectively regulated. The reason is the different sensitivities of the energy corresponding to K and Γ on the valence band to the strain due to the changes in different orbital overlaps. The tensile strain can effectively improve the flexibility of monolayers CrX2, which provides a possibility for the application of flexible electronic devices. Furthermore, the tensile strain can improve the piezoelectric strain coefficient of monolayers CrX2. Using Slacks formulation, we calculate the lattice thermal conductivity, and the tensile biaxial strain can reduce the lattice thermal conductivity. Our research provides a strategy to enhance the piezoelectric and flexible electronic applications and decrease the lattice thermal conductivity, which can benefit the thermoelectric applications.

Role of thrombospondin-1 in high-salt-induced mesenteric artery endothelial impairment in rats.

The matrix glycoprotein thrombospondin-1 (THBS1) modulates nitric oxide (NO) signaling in endothelial cells. A high-salt diet induces deficiencies of NO production and bioavailability, thereby leading to endothelial dysfunction. In this study we investigated the changes of THBS1 expression and its pathological role in the dysfunction of mesenteric artery endothelial cells (MAECs) induced by a high-salt diet. Wild-type rats, and wild-type and Thbs1-/- mice were fed chow containing 8% w/w NaCl for 4 weeks. We showed that a high salt diet significantly increased THBS1 expression and secretion in plasma and MAECs, and damaged endothelium-dependent vasodilation of mesenteric resistance arteries in wild-type animals, but not in Thbs1-/- mice. In rat MAECs, we demonstrated that a high salt environment (10-40 mM) dose-dependently increased THBS1 expression accompanied by suppressed endothelial nitric oxide synthase (eNOS) and phospho-eNOS S1177 production as well as NO release. Blockade of transforming growth factor-ß1 (TGF-ß1) activity by a TGF-ß1 inhibitor SB 431542 reversed THBS1 up-regulation, rescued the eNOS decrease, enhanced phospho-eNOS S1177 expression, and inhibited Smad4 translocation to the nucleus. By conducting dual-luciferase reporter experiments in HEK293T cells, we demonstrated that Smad4, a transcription promoter, upregulated Thbs1 transcription. We conclude that THBS1 contributes to endothelial dysfunction in a high-salt environment and may be a potential target for treatment of high-salt-induced endothelium dysfunction.

A qualitative study on inner experience of self-management behavior among elderly patients with type 2 diabetes in rural areas.

BACKGROUND: As a chronic metabolic disease, diabetes poses a serious threat to human health and has become a major public health problem in China and worldwide. In 2020, 30% of Chinese people (aged ≥ 60 years) reported having diabetes mellitus. Moreover, individuals with diabetes living in rural areas face a significantly higher mortality risk compared to those in urban areas. In this study, we explored the inner experience of self-management behaviors in elderly patients with type 2 diabetes in rural areas to inform targeted interventions. METHODS: A phenomenological research design was used to explore the inner experience of self-management in rural elderly diabetes. Ten elderly diabetic patients were sampled from December 2022 to March 2023 in rural areas of Yangcheng County, Jincheng City, ShanXi Province, China. The seven-step Colaizzi phenomenological was used to analyze the interview data and generate themes. RESULTS: Four themes emerged: "Insufficient self-management cognition", "Negative self-management attitude", "Slack self-management behavior", and "No time for self-management". CONCLUSION: The level of self-management among elderly patients with type 2 diabetes in rural areas is low. Healthcare professionals should develop targeted interventions aimed at enhancing their cognitive levels, modifying their coping styles, and improving their self-management abilities to improve their quality of life.

Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL-35 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T-cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL-35-mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL-35, a colitis model was successfully induced by giving BALB/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia/IL-35, empty plasmid-transformed Pichia (Pichia/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL-35 treatment was detected. After administration of Pichia/IL-35, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia/IL-35 treatment group was alleviated. Notably, Pichia/IL-35 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL-6 in the colon. With Pichia/IL-35 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. In vitro experiments, IL-35 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia/IL-35 group also expressed more TCPTP than that of the untreated group and the Pichia/0 group.

A Review on Traditional Uses, Phytochemistry, Pharmacology and Clinical Application of Tinospora sinensis (Lour.) Merr.

Tinospora sinensis (T. sinensis), whose Tibetan name is "Lezhe", as a traditional medicine, is widely distributed in China, India and Sri Lanka. It is used for the treatment of rheumatic arthralgia, sciatica, lumbar muscle strain and bruises. Research over the previous decades indicated that T. sinensis mainly contains terpenes, lignans, alkaloids, phenol glycosides and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, analgesic, immunosuppressive, anti-aging, anti-radiation, anti-leishmania and liver protection have been reported. However, the scholar's research on the pharmacodynamic material basis of T. sinensis is relatively weak. Data regarding many aspects such as links between the traditional uses and bioactivities, pharmacokinetics, and quality control standard of active compositions is still limited and need more attention. This review reports a total of 241 compounds, the ethnopharmacology and clinical application of T. sinensis, covering the literature which were searched by multiple databases including Web of Science, PubMed, Google Scholar, Science Direct, CNKI and other literature sources from 1996 to date, with a view to provide a systematic and insightful reference and lays a foundation and inspiration for the application and further in-depth research of T. sinensis resources.

Biomechanism of abnormal stress on promoting osteoarthritis of temporomandibular joint through Piezo1 ion channel.

OBJECTIVE: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). METHODS: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte. RESULTS: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F-actin. CONCLUSIONS: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA.

A Portable Electrochemical Dopamine Detector Using a Fish Scale-Derived Graphitized Carbon-Modified Screen-Printed Carbon Electrode.

In this paper, a highly conductive alkali-activated graphitized carbon (a-GC) was prepared using tilapia fish scales as precursors through enzymolysis, activation and pyrolytic carbonization methods. The prepared a-GC was modified on the surface of a screen-printed carbon electrode to construct a flexible portable electrochemical sensing platform, which was applied to the differential pulse voltametric detection of dopamine (DA) using a U-disk electrochemical workstation combined with a smart phone and Bluetooth. The prepared a-GC possesses good electrical conductivity, a large specific surface area and abundant active sites, which are beneficial for the electrooxidation of DA molecules and result in excellent sensitivity and high selectivity for DA analysis. Under the optimal conditions, the oxidation peak current of DA increased gradually, with its concentrations in the range from 1.0 µmol/L to 1000.0 µmol/L, with the detection limit as low as 0.25 µmol/L (3S/N). The proposed sensor was further applied to the determination of DA in human sweat samples, with satisfactory results, which provided an opportunity for developing noninvasive early diagnosis and nursing equipment.

Human Fis1 regulates mitochondrial dynamics through inhibition of the fusion machinery.

Mitochondrial dynamics is important for life. At center stage for mitochondrial dynamics, the balance between mitochondrial fission and fusion is a set of dynamin-related GTPases that drive mitochondrial fission and fusion. Fission is executed by the GTPases Drp1 and Dyn2, whereas the GTPases Mfn1, Mfn2, and OPA1 promote fusion. Recruitment of Drp1 to mitochondria is a critical step in fission. In yeast, Fis1p recruits the Drp1 homolog Dnm1p to mitochondria through Mdv1p and Caf4p, but whether human Fis1 (hFis1) promotes fission through a similar mechanism as in yeast is not established. Here, we show that hFis1-mediated mitochondrial fragmentation occurs in the absence of Drp1 and Dyn2, suggesting that they are dispensable for hFis1 function. hFis1 instead binds to Mfn1, Mfn2, and OPA1 and inhibits their GTPase activity, thus blocking the fusion machinery. Consistent with this, disruption of the fusion machinery in Drp1-/- cells phenocopies the fragmentation phenotype induced by hFis1 overexpression. In sum, our data suggest a novel role for hFis1 as an inhibitor of the fusion machinery, revealing an important functional evolutionary divergence between yeast and mammalian Fis1 proteins.

Surpassing the limitation of a coherence length in lidar by digital coherence.

In this manuscript, we propose a digital coherent detection method to surpass the limitation of a coherent length on the detection range of a coherent lidar. This method rapidly reconstructs the laser phase noise utilizing the multi-channel delay self-homodyne and the generalized inverse of the system observation matrix. Subsequently, the reconstructed phase noise is utilized to expunge its perturbation onto the target information in the digital domain, thereby effectively surmounting the coherence length limitation. Through experimentation, the proposed method is verified to produce stable and high-quality interference even when the optical path difference between two beams exceeds 1000 times the coherence length. Additionally, the equivalent laser linewidth is compressed by 105 times.

STAT3 promotes migration and invasion of cholangiocarcinoma arising from choledochal cyst by transcriptionally inhibiting miR200c through the c-myb/MEK/ERK signaling pathway.

Signal transducer and activator of transcription 3 (STAT3) have been highlighted in cancer regulation. Its roles in Cholangiocarcinoma (CCA) arising from the choledochal cyst (CC) were unclear. Here, we attempted to elucidate the roles of STAT3 in CCA-CC and explore its mechanism. A total of 20 patients with CCA arising from CC, that underwent CC excision in the infant stage were included. The expressions of STAT3, miR200c and c-Myb in clinical samples were assessed by RT-qPCR and/or western blot. Their expression correlations in tumor tissues were evaluated by Pearson correlation analysis. Their roles in CCA cell migration and invasion were investigated by gene silence using siRNA or miRNA inhibitor mediated approach and MEK activator. The expression levels of EMT, metastasis and MEK/ERK pathway-related proteins were checked by western blot. The high expressions of STAT3 and c-Myb, and low expression of miR200c were detected in CCA samples. We defined the transcription inhibition of STAT3 in miR200c expression and the negative correlation between miR200c and c-Myb expression. Silence of STAT3 increased miR200c expression and retarded the migration and invasion of CCA cells, accompanied by decreased levels of Vimentin, N-cadherin, MMP2 and MMP9, and elevated expression of E-cadherin, resulting in inactivating MEK/ERK pathway. MiR200c inhibitor reversed the changes induced by STAT3 silence, which was restored by si-c-Myb. MEK activator significantly reversed the inactivation of the MEK/ERK pathway induced by si-STAT3+miR200c inhibitor+si-c-Myb. In summary, the silence of STAT3 suppressed metastasis and progression of CCA cells by regulating miR200c through the c-Myb mediated MEK/ERK pathway, suggesting STAT3 is the effective target for CCA arising from CC.

Hexagonal warping effect in the Janus group-VIA binary monolayers with large Rashba spin splitting and piezoelectricity.

In this paper, the electronic band structure, Rashba effect, hexagonal warping, and piezoelectricity of Janus group-VIA binary monolayers STe2, SeTe2, and Se2Te are investigated based on density functional theory (DFT). Due to the inversion asymmetry and spin-orbit coupling (SOC), the STe2, SeTe2 and Se2Te monolayers exhibit large intrinsic Rashba spin splitting (RSS) at the Γ point with the Rashba parameters 0.19 eV Å, 0.39 eV Å, and 0.34 eV Å, respectively. Interestingly, based on the k·p model via symmetry analysis, the hexagonal warping effect and a nonzero spin projection component Sz arise at a larger constant energy surface due to nonlinear k3 terms. Then, the warping strength λ was obtained by fitting the calculated energy band data. Additionally, in-plane biaxial strain can significantly modulate the band structure and RSS. Furthermore, all these systems exhibit large in-plane and out-of-plane piezoelectricity due to inversion and mirror asymmetry. The calculated piezoelectric coefficients d11 and d31 are about 15-40 pm V-1 and 0.2-0.4 pm V-1, respectively, which are superior to those of most reported Janus monolayers. Because of the large RSS and piezoelectricity, the studied materials have great potential for spintronic and piezoelectric applications.

Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors.

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G2/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC50 values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.

Association of HMGB1 levels in synovial fluid with the severity of temporomandibular joint osteoarthritis.

BACKGROUND: HMGB1 usually serves as a damage-associated molecular pattern (DAMP) molecule (also known as alarmin) that regulates the inflammatory and immune responses via different receptors or direct uptake. Numerous studies have reported the association between HMGB1 and inflammatory diseases; however, its role in temporomandibular joint (TMJ) osteoarthritis (OA) has not been elucidated. In this retrospective study, we aimed to investigate HMGB1 levels in the synovial fluid (SF) in patients with TMJOA and TMID, their correlation with TMJOA and TMID severity, and the therapeutic effect of sodium hyaluronate (hyaluronic acid, HA) on TMJOA. METHODS: SF samples were analyzed for 30 patients with TMJ internal derangement (TMJID) and TMJOA, along with visual analog scale (VAS) scores, radiographic stages, and mandibular functional limitations. The SF levels of HMGB1, IL-1ß, IL-18, PGE2, RAGE, TLR4, and iNOS were determined via an enzyme-linked immunosorbent assay. To evaluate the therapeutic effects of HA, pre-treatment and post-treatment clinical symptoms were also compared in patients of the TMJOA group who had received an intra-articular injection of HA. RESULTS: VAS and Jaw Functional Limitation Scale (JFLS) scores were significantly higher in the TMJOA group than in the TMNID group, as were SF levels of HMGB1, TLR4, IL-1ß, IL-18, PGE2, and iNOS. The synovial HMGB1 level was positively correlated with the VAS score (r = 0.5512, p = 0.0016) and mandibular functional limitations (r = 0.4684, p = 0.0054). The cut-off value for the HMGB1 level as a diagnostic biomarker was 986.8 pg/ml. The SF level of HMGB1 yielded an area under the curve value (AUC) of 0.8344 for predicting TMJOA. HA alleviated TMJ disorders by significantly reducing the VAS score and improving the maximum extent of mouth opening in both the TMJID and TMJOA groups (p < 0.05). Moreover, patients in both the TMJID and TMJOA groups exhibited significant improvement in the JFLS score following HA treatment. CONCLUSIONS: Our results indicate that HMGB1 is a potential marker for predicting the severity of TMJOA. Intra-articular HA injection exerts a positive therapeutic effect on TMJOA; however, further investigations are warranted to validate its therapeutic effect in the late phase of visco-supplementation treatment.

Analysis of Traditional Chinese Medicine Constitution Types Among Adult Urolithiasis Patients in Wuhu, China.

Objective: This study aims to analyze the correlation between urinary calculi formation and Traditional Chinese Medicine (TCM) constitution among individuals in Wuhu. Methods: This retrospective study was conducted at our hospital from December 2020 to December 2021. A total of 140 cases were selected for the study population. The patients underwent thorough clinical and statistical analysis, and their TCM constitution classification was determined based on TCM constitution theory. Additionally, the study assessed the urinary stone composition of these 140 patients using the SUN-3G intelligent stone analyzer. Results: Among the 140 patients, the largest group comprised patients with a peaceful constitution, accounting for 36.43%. The second largest group, at 23.57%, included patients with constitution type A (peaceful + any other TCM constitution). Following that, patients with constitution type A G (Yang deficiency + any other TCM constitution) represented the third largest group at 7.14%. Conclusions: The majority of patients demonstrated a constitution characterized by peace and substance. Therefore, it is imperative to allocate medical resources strategically to enhance the effectiveness of Traditional Chinese Medicine syndrome differentiation in treatment.

Investigation of Morphologic Changes in Temporomandibular Joint With Anterior Disk Displacement Based on 3-Dimensional Reconstructive Imaging.

The objective of this study was to measure the association between the disk position and condylar alteration in patients diagnosed with anterior disk displacement (ADD) of temporomandibular joint (TMJ). A retrospective cross-sectional study was designed, dividing into 4 groups: normal articular disk position (NADP) of unilateral ADD patients (n=10), ADD with reduction (ADDwR, n=16), ADD without reduction (ADDwoR, n=24), and healthy volunteers (HV, n=30) based on magnetic resonance imaging and cone-beam computed tomography. After morphologic parameters were calculated from 3-dimensional reconstructive images, differences in parameters with respect to ADD status were tested with analysis of variance and Fisher least significant difference multiple comparisons were performed. Condylar volume of ADDwR, ADDwoR, NADP, and HVs were 1768.29±404.19, 1467.13±438.20, 1814.48±753.60, and 1914.66±476.48 mm, respectively, showing a significant downward trend from healthy disk to a displaced one ( P <0.05). Same trend also found in condylar superficial area, with the condylar superficial area of the ADDwR, ADDwoR, NADP, and HVs were 842.56±138.78 mm, 748.52±157.42 mm, 842.87±263.00 mm, and 892.73±164.19 mm, respectively. From NADP to ADDwR to ADDwoR, superior joint space (SJS) was declined, [SJS (NADP) (2.10±0.91 mm) > SJS (ADDwR) (1.85±0.61 mm) > SJS (ADDwoR) (1.50±0.50 mm), P =0.034]; medial joint space was significantly associated with the different disk displacement types ( P(HV-ADDwR) =0.001; P(HV-ADDwoR) =0.021; P(NADP-ADDwR) =0.022; P(ADDwR-ADDwoR) =0.001). Our findings suggest that condylar volume and superficial area, and superior and medial joint space, albeit with a small sample size, are significantly associated with different disk displacement types, detection of which might therefore be worth exploring for assessing ADD.