Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway.

Diabetic nephropathy (DN), a severe complication of diabetes, is widely recognized as a primary contributor to end-stage renal disease. Recent studies indicate that the inflammation triggered by Toll-like receptor 4 (TLR4) is of paramount importance in the onset and progression of DN. TLR4 can bind to various ligands, including exogenous ligands such as proteins and polysaccharides from bacteria or viruses, as well as endogenous ligands such as biglycan, fibrinogen, and hyaluronan. In DN, the expression or release of TLR4-related ligands is significantly elevated, resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways. This process is closely associated with the progression of DN. Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases. Various types of natural compounds, including alkaloids, flavonoids, polyphenols, terpenoids, glycosides, and polysaccharides, have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway. In this review, we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway. We specifically highlight the potential of compounds such as curcumin, paclitaxel, berberine, and ursolic acid to inhibit the TLR4 signaling pathway, which provides an important direction of research for the treatment of DN.

Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.

Niemann-Pick disease type C1 (NP-C1) is a rare and devastating recessive inherited lysosomal lipid and cholesterol storage disorder caused by mutations in the NPC1 or NPC2 gene. These two proteins bind to cholesterol and cooperate in endosomal cholesterol transport. Characteristic clinical manifestations of NP-C1 include hepatosplenomegaly, progressive neurodegeneration, and ataxia. While the rarity of NP-C1 presents a significant obstacle to progress, researchers have developed numerous potential therapeutic approaches over the past two decades to address this condition. Various methods have been proposed and continuously improved to slow the progression of NP-C1, although they are currently at an animal or clinical experimental stage. This overview of NP-C1 therapy will delve into different theoretical treatment strategies, such as small molecule therapies, cell-based approaches, and gene therapy, highlighting the complex therapeutic challenges associated with this disorder.

The relationship between lung CT features and serum cryptococcal antigen titers in localized pulmonary cryptococcosis patients.

BACKGROUND: To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. METHODS: A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. RESULTS: A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (ß, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (ß, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. CONCLUSION: In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.

A Recyclable Ionogel with High Mechanical Robustness Based on Covalent Adaptable Networks.

Ionogels are an emerging class of soft materials for flexible electronics, with high ionic conductivity, low volatility, and mechanical stretchability. Recyclable ionogels are recently developed to address the sustainability crisis of current electronics, through the introduction of non-covalent bonds. However, this strategy sacrifices mechanical robustness and chemical stability, severely diminishing the potential for practical application. Here, covalent adaptable networks (CANs) are incorporated into ionogels, where dynamic covalent crosslinks endow high strength (11.3 MPa tensile strength), stretchability (2396% elongation at break), elasticity (energy loss coefficient of 0.055 at 100% strain), and durability (5000 cycles of 150% strain). The reversible nature of CANs allows the ionogel to be closed-loop recyclable for up to ten times. Additionally, the ionogel is toughened by physical crosslinks between conducting ions and polymer networks, breaking the common dilemma in enhancing mechanical properties and electrical conductivity. The ionogel demonstrates robust strain sensing performance under harsh mechanical treatments and is applied for reconfigurable multimodal sensing based on its recyclability. This study provides insights into improving the mechanical and electrical properties of ionogels toward functionally reliable and environmentally sustainable bioelectronics.

Test-time Training for Hyperspectral Image Super-resolution.

The progress on Hyperspectral image (HSI) super-resolution (SR) is still lagging behind the research of RGB image SR. HSIs usually have a high number of spectral bands, so accurately modeling spectral band interaction for HSI SR is hard. Also, training data for HSI SR is hard to obtain so the dataset is usually rather small. In this work, we propose a new test-time training method to tackle this problem. Specifically, a novel self-training framework is developed, where more accurate pseudo-labels and more accurate LR-HR relationships are generated so that the model can be further trained with them to improve performance. In order to better support our test-time training method, we also propose a new network architecture to learn HSI SR without modeling spectral band interaction and propose a new data augmentation method Spectral Mixup to increase the diversity of the training data at test time. We also collect a new HSI dataset with a diverse set of images of interesting objects ranging from food to vegetation, to materials, and to general scenes. Extensive experiments on multiple datasets show that our method can improve the performance of pre-trained models significantly after test-time training and outperform competing methods significantly for HSI SR.

Cell-based therapies reverse the heart failure-altered right ventricular proteome.

Background: Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression. We aimed to determine the proteomic response of diseased hearts to cell therapy. Methods: We utilized an animal model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics. Results: Proteomic profiling identified 1156 total proteins from the RV, of which 5.97% were significantly changed after PAB. This disease-altered proteome was responsive to cellular therapy, with 72% of the PAB-altered proteome being fully or partially reversed by MSC therapy. This was followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%). Systems biology and bioinformatics analysis showed MSC, nCPC, or ES-CPC cell therapy is associated with a decrease in predicted adverse cardiac effects. We also observed an effect of cell therapy on the non-altered RV proteome, however, this was associated with minor predicted pathological endpoints. Conclusions: Our data indicate MSCs, ES-CPCs, and nCPCs significantly reverse the PAB-altered proteome towards a pre-disease state. These results indicate cell-based therapies show promise in improving RV function after pressure overload through partial restoration of the disease-altered cardiac proteome.

The effects of all-trans retinoic acid on prednisolone-induced osteoporosis in zebrafish larvae.

Glucocorticoids (GCs) are extensively used as anti-inflammatory and immunosuppressive medications in the long-term treatment of rheumatic disorders, respiratory diseases, renal diseases, and organ transplantation. Prolonged use of GCs can reduce bone mineral density, leading to osteoporosis (Glucocorticoid Induced Osteoporosis, GIOP) and fracture. All-trans retinoic acid (ATRA) is an active vitamin A metabolite that regulates embryonic development and adult organ function. ATRA has been found in studies to enhance osteogenesis. To examine the interventional effects of ATRA on GIOP and the mechanisms of ATRA activities, we first performed bioinformatic analysis to identify potential gene targets of ATRA. Zebrafish larvae were recruited as experimental animals, and the frequently used GC, prednisolone, was administered to larvae to construct a GIOP model. We evaluated the influence of exogenous ATRA on the activities of bone metabolic enzymes, the expression of genes linked to osteoblasts and osteoclasts, and the restoration of bone mineral density and bone mass in GIOP zebrafish larvae. Furthermore, we studied the influence of RBM14, a transcriptional coactivator and negative reciprocal factor of ATRA, on the regulation of osteoblastic gene expression during the anti-GIOP process of ATRA using the morpholino knockdown approach. The findings of bone metabolic enzyme activity (alkaline phosphatase, ALP and tartrate-resistant acid phosphatase, TRAP) and expression assays of osteoblastic marker genes (Runx2a, Runx2b, SP7, Csf1a, RANKL, and CTSK) indicated that ATRA had bidirectional effects on osteogenesis. However, in the GIOP model, ATRA reversed the GIOP-induced osteoporosis phenotype by inhibiting the GIOP-induced suppression of osteoblastic metabolic enzyme (ALP) activities and osteoblastic marker gene expression (Runx2a, Runx2b, and SP7), and this antagonism was concentration-dependent. We also observed that ATRA inhibited RBM14 expression in zebrafish larvae, while ATRA alone and RBM14 knockdown showed a consistent induction of osteoblast marker gene expression, implying that ATRA's inhibitory effect on RBM14 expression may underlie ATRA's osteogenic effects. Based on these data, we postulated that ATRA may ameliorate GIOP by decreasing RBM14 expression, thereby enhancing osteoblastic marker gene expression.

Intelligent Song Recognition via a Hollow-Microstructure-Based, Ultrasensitive Artificial Eardrum.

Artificial ears with intelligence, which can sensitively detect sound-a variant of pressure-and generate consciousness and logical decision-making abilities, hold great promise to transform life. However, despite the emerging flexible sensors for sound detection, most success is limited to very simple phonemes, such as a couple of letters or words, probably due to the lack of device sensitivity and capability. Herein, the construction of ultrasensitive artificial eardrums enabling intelligent song recognition is reported. This strategy employs novel geometric engineering of sensing units in the soft microstructure array (to significantly reduce effective modulus) along with complex song recognition exploration leveraging machine learning algorithms. Unprecedented pressure sensitivity (6.9 × 103 kPa-1) is demonstrated in a sensor with a hollow pyramid architecture with porous slants. The integrated device exhibits unparalleled (exceeding by 1-2 orders of magnitude compared with reported benchmark samples) sound detection sensitivity, and can accurately identify 100% (for training set) and 97.7% (for test set) of a database of the segments from 77 songs varying in language, style, and singer. Overall, the results highlight the outstanding performance of the hollow-microstructure-based sensor, indicating its potential applications in human-machine interaction and wearable acoustical technologies.

[Mechanism of berberine in improving adipocytic IR by mediating BMAL1:CLOCK complex and regulating glucose and lipid metabolism].

To explore the action mechanism of berberine in improving adipocytic insulin resistance(IR) by mediating brain and muscle arnt-like 1(BMAL1): circadian locomotor output cycles kaput(CLOCK) complex and regulating glucose and lipid metabolism. After the IR-3T3-L1 adipocyte model was established by dexamethasone induction for 96 h, 0.5, 1, 5, 10, and 20 µmol·L~(-1) berberine was administered for 24 h. The glucose oxidase method and cell counting kit-8(CCK-8) were used to detect extracellular glucose content and cell viability, respectively. The triglyceride(TG) and glycerol contents were detected by enzyme colorimetry. Oil red O staining was used to detect lipid droplets, and fluorescence staining was used to detect Ca~(2+), mitochondrial structure, and reactive oxygen species(ROS). Adiponectin(ADPN), BMAL1, CLOCK, hormone-sensitive triglyceride lipase(HSL), carbohydrate-response element-binding protein(ChREBP), sterol regulatory element-binding protein 1C(SREBP-1C), peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α), carnitine palmitoyl transferase 1α(CPT1α), and peroxisome proliferator-activated receptor α(PPARα) were detected by Western blot(WB). Moreover, the nuclear localization of BMAL1 was detected by immunofluorescence. In addition, 20 µmol·L~(-1) CLK8 inhibitor was added to detect glucose consumption and BMAL1/ChREBP/PPARα protein. The results showed that berberine increased glucose consumption in IR-3T3-L1 adipocytes without affecting cell viability and reduced TG content. In addition, 5 µmol·L~(-1) berberine increased glycerol content and reduced lipid droplet accumulation due to enhanced lipolysis, while 10 µmol·L~(-1) berberine did not affect glycerol content, and fewer lipid droplets were observed due to enhanced lipolysis and glycerol utilization. Berberine improved mitochondrial function by reducing intracellular Ca~(2+) and ROS in IR-3T3-L1 adipocytes and upregulated PGC1α to improve the mitochondrial structure. The results also showed that berberine elevated ADPN to increase the insulin sensitivity of IR-3T3-L1 adipocytes, upregulated peripheral rhythm-related proteins BMAL1 and CLOCK, and strengthened the nuclear localization of BMAL1. In addition, berberine increased key lipolysis protein and lipid oxidation rate-limiting enzyme CPT1α and downregulated the key protein of TG synthesis, SREBP-1C. Moreover, ChREBP and PPARα in IR-3T3-L1 adipocytes were upregula-ted. All the above results suggested that berberine may transform glucose into lipids to enhance the hypoglycemic effect. By considering that CLK8 specifically inhibited the CLOCK acylation to modify BMAL1 and form complex, the results showed that the addition of CLK8 to the berberine group reduced glucose consumption, which suggested that berberine upregulated the formation of BMAL1:CLOCK complex to improve glucose metabolism. The addition of CLK8 to the berberine group upregulated BMAL1 but downregulated ChREBP and PPARα, which suggested that berberine mediated BMAL1:CLOCK complex for the regulation of glucose and lipid metabo-lism to improve adipocytic IR.

1,1'-Biolympicenyl: A Stable Non-Kekulé Diradical with a Small Singlet and Triplet Energy Gap.

Dimerization of delocalized polycyclic hydrocarbon radicals is a simple and versatile method to create diradicals with tailored electronic structures and accessible high-spin states. However, the synthesis is challenging, and the stability issue of the diradicals remains a concern. In this study, we present the synthesis of a stable non-Kekulé 1,1'-biolympicenyl diradical 1 using a protection-oxidation-protection strategy. Diradical 1 demonstrated exceptional stability, with a solution half-life time exceeding 3.5 years and a solid state thermal decomposition temperature above 300 °C. X-ray crystallographic analysis revealed its intersected molecular structure and tightly bound dimer configuration. A singlet ground state with a small singlet-triplet energy gap is consistently identified using electron paramagnetic resonance (EPR) and a superconducting quantum interference device (SQUID) in a rigid matrix, and the triplet state is thermally accessible at room temperature. The solution phase properties were systematically examined through EPR, absorption spectroscopy, and cyclic voltammetry, revealing a rotational motion in the slow-motion regime and multistage redox characteristics. This study presents an efficient synthetic and stabilization strategy for organic diradicals, enabling the development of various high-spin functional materials.

The critical role of Gαi3 in oral squamous cell carcinoma cell growth.

The identification of novel and effective therapeutic targets for oral squamous cell carcinoma (OSCC) is of paramount importance. This study investigates the expression, potential functions, and mechanistic insights of G protein inhibitory subunit 3 (Gαi3) in OSCC. Gαi3 is found to be upregulated in human OSCC tissues as well as in various primary and established OSCC cells. In different OSCC cells, silencing of Gαi3 through shRNA resulted in inhibited cell proliferation and migration, while also inducing apoptosis. Knockout (KO) of Gαi3 via the CRISPR/Cas9 method produced significant anti-cancer effects in OSCC cells. Conversely, ectopic overexpression of Gαi3 enhanced OSCC cell growth, promoting cell proliferation and migration. Gαi3 plays a crucial role in activating the Akt-mTOR signaling pathway in OSCC cells. Silencing or KO of Gαi3 led to decreased phosphorylation levels of Akt and S6K, whereas overexpression of Gαi3 increased their phosphorylation. Restoration of Akt-mTOR activation through a constitutively active mutant Akt1 mitigated the anti-OSCC effects induced by Gαi3 shRNA. In vivo, Gαi3 silencing significantly suppressed the growth of subcutaneous OSCC xenografts in nude mice, concomitant with inactivation of the Akt-mTOR pathway and induction of apoptosis. Collectively, these findings underscore the critical role of Gαi3 in OSCC cell growth both in vitro and in vivo.

Association between nontraditional lipid parameters and the risk of type 2 diabetes and prediabetes in patients with nonalcoholic fatty liver disease: from the national health and nutrition examination survey 2017-2020.

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder strongly linked to type 2 diabetes mellitus (T2DM). Understanding the predictive value of lipid parameters in identifying abnormal glucose metabolism in NAFLD patients is crucial for early intervention. Methods: This study analyzed data from the National Health and Nutrition Examination Survey(NHANES) database (2017-2020) involving 1066 NAFLD patients. Participants were categorized into three groups: T2DM (n=414), prediabetes mellitus (pre-DM) (n=507), and normoglycemia (NG) (n=145). Traditional lipid parameters [triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and nontraditional lipid parameters [atherogenic index of plasma (AIP), residual cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C)] were evaluated for their association with T2DM and pre-DM. Results: Elevated TG levels were significantly associated with an increased risk of T2DM and pre-DM, whereas high HDL-C demonstrated a protective effect. Among nontraditional lipid parameters, increased AIP and RC were most strongly associated with T2DM risk, while high non-HDL-C was best associated with the development of pre-DM. Stratified analyses revealed that these associations were stronger in younger, non-obese, smoking, and female NAFLD patients. Conclusion: Nontraditional lipid parameters, particularly AIP and RC, show superior predictive value over traditional lipid parameters in identifying abnormal glucose metabolism in NAFLD patients. Incorporating these novel biomarkers into clinical practice could enhance early detection and prevention strategies for T2DM and pre-DM in this high-risk population.

Bone marrow-derived mesenchymal stem cell-derived exosome-loaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage.

BACKGROUND: Diabetic intracerebral hemorrhage (ICH) is a serious complication of diabetes. The role and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomes (BMSC-exo) in neuroinflammation post-ICH in patients with diabetes are unknown. In this study, we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation. AIM: To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage. METHODS: BMSC-exo were isolated from mouse BMSC media. This was followed by transfection with microRNA-129-5p (miR-129-5p). BMSC-exo or miR-129-5p-overexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucose-affected BV2 cells for in vitro analyses. The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1 (HMGB1). Quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors, such as HMGB1, interleukin 6, interleukin 1ß, toll-like receptor 4, and tumor necrosis factor α. Brain water content, neural function deficit score, and Evans blue were used to measure the neural function of mice. RESULTS: Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery. MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation. Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases. Furthermore, we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA. CONCLUSION: We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes, thereby improving the neurological function of the brain.

Associations between cuprotosis-related genes and the spectrum of metabolic dysfunction-associated fatty liver disease: An exploratory study.

AIMS: To explore the associations between cuprotosis-related genes (CRGs) across different stages of liver disease in metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We analysed several bulk RNA sequencing datasets from patients with MAFLD (n = 331) and MAFLD-related HCC (n = 271) and two MAFLD single-cell RNA sequencing datasets. To investigate the associations between CRGs and MAFLD, we performed differential correlation, logistic regression and functional enrichment analyses. We also validated the findings in an independent Wenzhou PERSONS cohort of MAFLD patients (n = 656) used for a genome-wide association study (GWAS). RESULTS: GLS, GCSH and ATP7B genes showed significant differences across the MAFLD spectrum and were significantly associated with liver fibrosis stages. GLS was closely associated with fibrosis stages in patients with MAFLD and those with MAFLD-related HCC. GLS is predominantly expressed in monocytes and T cells in MAFLD. During the progression of metabolic dysfunction-associated fatty liver to metabolic-associated steatohepatitis, GLS expression in T cells decreased. GWAS revealed that multiple single nucleotide polymorphisms in GLS were associated with clinical indicators of MAFLD. CONCLUSIONS: GLS may contribute to liver inflammation and fibrosis in MAFLD mainly through cuprotosis and T-cell activation, promoting the progression of MAFLD to HCC. These findings suggest that cuprotosis may play a role in MAFLD progression, potentially providing new insights into MAFLD pathogenesis.

Effect of chickpea protein modified with combined heating and high-pressure homogenization on enhancing the gelation of reduced phosphate myofibrillar protein.

The effects of chickpea protein (CP) modified by heating and/or high-pressure homogenization (HPH) on the gelling properties of myofibrillar protein under reduced phosphate conditions (5 mM sodium triphosphate, STPP) were investigated. The results showed that heating and HPH dual-modified CP could decrease the cooking loss by 29.57 %, elevate the water holding capacity by 17.08 %, and increase the gel strength by 126.88 %, which conferred myofibrillar protein with gelation performance comparable with, or even surpassing, that of the high-phosphate (10 mM STPP) control. This gelation behavior improvement could be attributed to enhanced myosin tail-tail interactions, decreased myosin thermal stability, elevated trans-gauche-trans disulfide conformation, strengthened hydrophobic interactions and hydrogen bonding, the uncoiling of α-helical structures, the formation of well-networked myofibrillar protein gel, and the disulfide linkages between the myosin heavy chain, actin, and CP subunits. Therefore, the dual-modified CP could be a promising phosphate alternative to develop healthier meat products.

Biodegradable Piezoelectric-Conductive Integrated Hydrogel Scaffold for Repair of Osteochondral Defects.

Osteochondral injury is a prevalent condition for which no specific treatment is currently available. This study presents a piezoelectric-conductive scaffold composed of a piezoelectric cartilage-decellularized extracellular matrix (dECM) and piezoelectric-conductive modified gelatin (Gel-PC). The piezoelectricity of the scaffold is achieved through the modification of diphenylalanine (FF) assembly on the pore surface, while the conductive properties of scaffold are achieved by the incorporating poly(3,4-ethylenedioxythiophene). In vitro experiments demonstrate that bone marrow mesenchymal stem cells (BMSCs) undergo biphasic division during differentiation. In vivo studies using a Parma pig model of osteochondral defects demonstrate that the piezoelectric-conductive scaffold exhibits superior reparative efficacy. Notably, the generation of electrical stimulation is linked to joint movement. During joint activity, mechanical forces compress the scaffold, leading to deformation and the subsequent generation of an electric potential difference. The positive charges accumulated on the upper layer of the scaffold attract BMSCs, promoting their migration to the upper layer and chondrogenic differentiation. Meanwhile, the negative charges in the lower layer induce the osteogenic differentiation of BMSCs. Overall, this piezoelectric-conducive scaffold provides a promising platform for the effective repair of osteochondral defects.

Review effects of radiation treatment on HPV-related vulvar cancer: a meta-analysis and systematic review.

Objective: Vulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy. Methods: A meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957). Results: We identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,<0.01). Meanwhile, the complete remission rate after radiotherapy was higher for HPV-associated vulvar cancer patients (M-H=4.02, 95% CI: 1.87-8.61, P=0.0003), and the local control rate was better (HR=1.90, 95% CI: 1.15-3.15, P=0.01), exhibiting a reduced incidence of relapse within the field of study (HR=0.21, 95% CI: 0.10-0.42, P<0.001). Conclusion: In comparison to HPV-independent vulvar squamous cell carcinoma, patients with HPV-associated vulvar cancer exhibit higher sensitivity to radiotherapy, with a significant difference in prognosis. Further research should investigate the mechanisms underlying this high sensitivity to radiotherapy caused by HPV, and should be evaluated using high-quality randomized controlled trials.

Bioactive polyketides and tryptophol alkaloids from the endophytic fungus Botryosphaeria dothidea LE-07 of Chinese tulip tree.

Two new tetraketide-derived phenol rhamnosides [botryrhamnosides A (1) and B (2)] and a new rhamnosylated tryptophol alkaloid (botryrhamnoside C, 3), along with seven related known compounds (4-10) were isolated from the solid culture of Botryosphaeria dothidea LE-07, an endophytic fungus residing in the leaves of the rare medicinal plant Chinese tulip tree (Liriodendron chinense). Their structures with the absolute configurations were determined by a combination of spectroscopy methods, comparing specific rotations, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 are rare tetraketide-derived resorcinols incorporating a l-rhamnose moiety, while 3 represents the first example of rhamnose-bound tryptophol derivatives produced by microorganisms. These metabolites were evaluated in vitro for their antimicrobial and anti-neuroinflammation activities. The rhamnosylated derivatives 1-5 displayed potent antibacterial activity against Escherichia coli, with MIC values in the range of 8-16 µg/mL. Compound 2 attenuated neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 microglial cells, by decreasing the level of pro-inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6)] and down-regulating the mRNA expression of inducible nitric oxide synthase (iNOS). In addition, compound 8 exhibited remarkable inhibitory effect against the ATP-citrate lyase (ACL), an emerging drug target for hyperlipidemia and related glycolipid metabolic disorders, with an IC50 value of 5.32 µM.

Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.

Cell death is of great significance in maintaining tissue homeostasis and bodily functions. With considerable research coming to the fore, it has been found that programmed cell death presents in multiple modalities in the body, which is not only limited to apoptosis, but also can be divided into autophagy, pyroptosis, ferroptosis, mitotic catastrophe, entosis, netosis, and other ways. Different forms of programmed cell death have disparate or analogous characteristics with each other, and their occurrence is accompanied by multiple signal transduction and the role of a myriad of regulatory factors. In recent years, scholars across the world have carried out considerable in-depth research on programmed cell death, and new forms of cell death are being discovered continually. Concomitantly, the mechanisms of intricate signaling pathways and regulators have been discovered. More critically, cancer cells tend to choose distinct ways to evade cell death, and different tumors adapt to different manners of death. Therefore, targeting the cell death network has been regarded as an effective tumor treatment strategy for a long time. The objective of our paper is to review the signaling pathways and gene regulation in several typical types of programmed cell death and their correlation with cancer.