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Objectives: Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and dental abnormalities. Tooth agenesis has been reported in CSS patients, but the mechanisms regulating this syndromic tooth agenesis remain largely unknown. This study aims to identify the pathogenic mutation of CSS presenting tooth genesis and explore potential regulatory mechanisms. Materials and methods: We utilized whole-exome sequencing to identify variants in a CSS patient, followed by Sanger validation. In silico analysis including conservation analysis, pathogenicity predictions, and 3D structural assessments were carried out. Additionally, single-cell RNA sequencing and fluorescence in situ hybridization (FISH) were applied to explore the spatio-temporal expression of Sox4 expression during murine tooth development. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to examine the functional role of SOX4. Results: A novel de novo SOX4 missense mutation (c.1255C > G, p.Leu419Val) was identified in a Chinese CSS patient exhibiting tooth agenesis. Single-cell RNA sequencing and FISH further verified high expression of Sox4 during murine tooth development, and WGCNA confirmed its central role in tooth development pathways. Enriched functions included cell-substrate junctions, focal adhesion, and RNA splicing. Conclusions: Our findings link a novel SOX4 mutation to syndromic tooth agenesis in CSS. This is the first report of SOX4 missense mutation causing syndromic tooth agenesis. Clinical Relevance: This study not only enhances our understanding of the pathogenic mutation for syndromic tooth agenesis but also provides genetic diagnosis and potential therapeutic insights for syndromic tooth agenesis. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 μg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of repeat transurethral resection on restaging, preventing tumor recurrence and progression in high-risk non-muscle invasive bladder cancer patients who received initial en bloc resection. Methods and patients: We reviewed retrospectively the clinical records of 330 consecutive patients who received en bloc resection for non-muscle invasive bladder cancer. Eligible patients with and without repeat transurethral resection were matched 1:1 by propensity score. Important covariates were balanced between the two groups. We compared the recurrence-free survival, progression-free survival, recurrence rate, and progression rate between groups. And the perioperative results regarding residual tumors and the safety of the repeat resection were also evaluated. Results: Finally, there are 245 patients included in our analysis with a median follow-up duration of 19 months (range 3–50). Detrusor muscle presented in 244 (99.6%) specimens at initial en bloc resection. And among them, 30 (12.2%) patients had undergone a repeat resection and 215 (87.8%) did not. After 1:1 propensity score matching, 30 pairs were further analyzed.No case of upstaging was identified in repeat resection. During the follow-up, recurrence was observed in 5 (16.7%) and 7 (23.3%) patients in reresection group and non-reresection group, respectively. And progression was found only in 1 (3.3%) patient in each group. The 1-year recurrence-free survival estimates were comparable (86.7% vs 83.3%, p = 0.86) between groups. Conclusion: Our study demonstrates that repeat resection after initial transurethral en bloc resection for bladder tumor appears not to improve staging accuracy, recurrence, and progression. [ABSTRACT FROM AUTHOR]

Background: Carpal tunnel syndrome is a common compressive neuropathy. There is a lack of comprehensive studies evaluating carpal tunnel release (CTR) complications in Australia. This study aimed to evaluate complication rates associated with open and endoscopic CTR in an Australian population, and to identify associated risk factors. Methods: Retrospective cohort study of 1287 CTR from 2015 to 2020. Methods of release were endoscopic, open and surgery concomitant with synovectomy or other. Outcomes included wound infection, dehiscence, nerve injury, complex regional pain syndrome, incomplete release, and re‐operation. Statistical analysis included Chi‐squared test, Fisher's exact test, Odds ratio and logistic regression. Results: There were 71 total complications (5.5%), including 35 Clavien–Dindo IIIb complications. There was no difference in complication rates for endoscopic (3.3%) versus open (8.3%) CTR (P = 0.18). The overall rate of complications was higher in CTR with concomitant surgery (8.5%) compared to CTR alone (5.2%), though this was not statistically significant (P = 0.058). There was no association between rates of complications and immune suppression (p = 0.55), rheumatoid disease (P = 0.61), or smoking status (P = 0.72). Diabetes mellitus was associated with an increased risk of Clavien‐Dindo IIIb complications (P = 0.028, OR 2.15, 95% CI 1.07–4.32). There was no association between surgical experience and complication rate (P = 0.55). Conclusion: Open and endoscopic CTR surgeries have similar rates of complications. Diabetes is associated with higher rates of Clavien‐Dindo IIIb complications. Identification of high‐risk patients allows for the application of risk‐mitigation strategies in the perioperative setting. [ABSTRACT FROM AUTHOR]

International guidelines recommend repeat transurethral resection of bladder tumors (reTURB) for selected patients with high-risk non-muscle invasive bladder cancer to remove possible residual tumors, restage tumors and improve the therapeutic outcome. However, most evidence supporting the benefits of reTURB is from conventional TURB. The role of reTURB in patients receiving initial En bloc resection of bladder tumor (ERBT) is still unknown. PubMed, Embase, Web of Science, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were systematically searched. Finally, this systematic review and meta-analysis included twelve articles, including 539 patients. The rates of residual tumor and tumor upstaging detected by reTURB after ERBT were 5.9% (95%CI, 2.0%–11.1%) and 0.0% (95%CI, 0.0%–0.5%), respectively. Recurrence-free survival, tumor recurrence and progression were comparable between patients with and without reTURB after initial ERBT. The pooled hazard ratios of 1-year, 2-year, 3-year and 5-year recurrence-free survival were 0.74 (95%CI, 0.36–1.51; p = 0.40), 0.76 (95%CI, 0.45–1.26; p = 0.28), 0.83 (95%CI, 0.53–1.32; p = 0.43) and 0.83 (95%CI, 0.56–1.23; p = 0.36), respectively. The pooled relative risks of recurrence and progression were 0.87 (95%CI, 0.64–1.20; p = 0.40) and 1.11 (95%CI, 0.54–2.32; p = 0.77), respectively. Current evidence demonstrates that reTURB after ERBT for bladder cancer can detect relatively low rates of residual tumor and tumor upstaging and appears not to improve either recurrence or progression. [ABSTRACT FROM AUTHOR]

Space station is under the increasing threaten caused by large amount of space debris on Earth orbit. Besides traditional active and passive defense measures, it is urgent to study active close-in defense strategy for protecting space station from space debris. In this paper, an active close-in defense mode is proposed for a space station based on a flexible and deployable proximity defense shield, while a hybrid procedure is formulated to optimize the on-orbit placement of the shield. First, an active close-in defense scheme for a space station is proposed. Second, the proximity defense process is modeled including orbit propagation and impact momentum transfer. Third, the orbital spatio-temporal evolution of the space debris and the proximity defense shield during the defense process are transformed into a multi-dimensional space probability distribution using the Poincaré section and the Gaussian mixture model. Then, based on probability optimization, the on-orbit placement of the proximity defense shield is optimized for protecting a space station from tiny space debris. Finally, comparison simulations demonstrate the effectiveness and feasibility of the proposed technique. • An innovative space debris close-in defense mode for space station is presented. • An hybrid procedure is proposed to optimize on-orbit placement of proximity defense shield. • The main outcome is the determination of the optimal position of the shield in orbit for debris defense. [ABSTRACT FROM AUTHOR]

Under the guidance of the traditional pattern differentiation system of wei, qi, ying and blood, most TCM doctors believe that a critical condition appears when the pathogenic factor enters the blood level in the development of warm diseases, while ignore that it could also occur in a qi level pattern. Based on Professor Jiang Liangduo's new view that " severe warm diseases could occur at qi level" developed based on his experience in the prevention and treatment of Corona Virus Disease 2019 (COVID-19), combined with the theory of " differentiation and treatment based on one ' s body condition", this paper elaborates on the theoretical basis, pathogenesis evolution, prevention and treatment method of severe warm diseases at qi level, and points out that the occurrence of severe warm diseases at qi level is closely related to the physiological dysfunction of lung qi. Thus, this paper summarizes the pathogenesis of severe COVID-19 cases at qi level as follows: dampness toxic epidemic pathogenic factors attack the lung, damaging the lung and making it unable to disperse and descend qi and body fluids as normal. The debilitated lung qi can neither promote body fluid circulation nor constrain fluids, which in turn leads to the expiry of lung qi. Correspondingly, the main principle of treatment is to diffuse the lung, replenish lung qi and constrain body fluids. [ABSTRACT FROM AUTHOR]

The C‐terminal domain (CTD) of RNA polymerase II serves as a binding platform for numerous enzymes and transcription factors involved in nascent RNA processing and the transcription cycle. The S2, S5‐phosphorylated CTD is recognized by the transcription factor SCAF4, which functions as a transcription anti‐terminator by preventing early mRNA transcript cleavage and polyadenylation. Here, we measured the binding affinities of differently modified CTD peptides by hSCAF4 and solved the complex structure of the hSCAF4‐CTD‐interaction domain (CID) bound to a S2, S5‐quadra‐phosphorylated CTD peptide. Our results revealed that the S2, S5‐quadra‐phosphorylated CTD peptide adopts a trans conformation and is located in a positively charged binding groove of hSCAF4‐CID. Although hSCAF4‐CID has almost the same binding pattern to the CTD as other CID‐containing proteins, it preferentially binds to the S2, S5‐phosphorylated CTD. Our findings provide insight into the regulatory mechanism of hSCAF4 in transcription termination. [ABSTRACT FROM AUTHOR]

A novel sandwich-type electrochemiluminescence (ECL) immunosensor was successfully fabricated for the ultrasensitive detection of avian leukosis virus subgroup J (ALV-J). The immunosensor used a glassy carbon electrode decorated with gold nanoparticles (Au NPs), primary antibodies (Ab1) and bovine serum albumin as the sensor platform. For the signal label, three-dimensional flower-like MnO2 clusters modified with polyethyleneimine and palladium nanoparticles (MnO2–PEI–Pd nanocomposite) were used as the novel carrier of Ru(bpy)3Cl2 and secondary antibodies (Ab2). Under optimal conditions, the ECL immunosensor offered a linear relationship between the ECL signal and the logarithm of the ALV-J concentration in the range from 101.98 to 104.30 TCID50/mL with a detection limit of 101.90 TCID50/mL (based upon a signal-to-noise ratio of 3). In addition, the immunosensor showed excellent stability, selectivity and reproducibility, thus offering an effective tool for the quantitative detection of ALV-J in clinical applications. [ABSTRACT FROM AUTHOR]

Abstract A novel sandwich-type electrochemical immunosensor was fabricated for the ultrasensitive detection of avian leukosis virus subgroup J (ALV-J). The immunosensor used a β-cyclodextrin-nanogold-ferrocene (β-CD-AuNP-Fc) host-guest complex as the label and a perylene-3,4,9,10-tetracarboxylic acid functional graphene nanocomposite (GR-PTCA) as the sensor platform. The abundant polycarboxylic sites of GR-PTCA facilitated the binding of primary antibodies (Ab 1), whilst the excellent electrical conductivity of GR-PTCA promoted electron transfer. Immobilization of β-CD directly onto secondary antibodies (Ab 2) via covalent bonding allowed strong binding of ferrocene-decorated gold nanoparticles (Fc-Au NP), thereby amplifying the immunosensor signal. Under optimized testing conditions, the reduction current of ferrocene exhibited a linearly dependence on the ALV-J titer in the concentration range of 102.0-104.0 TCID 50 /mL, with a low detection limit of 101.93 TCID 50 /mL. Furthermore, the immunosensor demonstrated high sensitivity, good reproducibility, reusability and stability, suggesting excellent potential for the quantitative detection of ALV-J in clinical applications. Graphical abstract The study reports the successful fabrication of a novel electrochemical immunosensor for the detection of ALV-J, which used a β-CD-AuNP-Fc host-guest complex as the label and a GR-PTCA nanocomposite as the sensor platform. Immobilization of β-CD directly onto secondary antibodies (Ab 2) via covalent bonding allowed strong binding of ferrocene-decorated gold nanoparticles (Fc-Au NP), thereby amplifying the immunosensor signal. Image 1 Highlights • A novel signal amplifying strategy was proposed for electrochemical immunosensing ALV-J. • Immobilization of β-CD directly onto Ab 2 simplified the sensor fabrication process. • The strong binding of β-CD and Fc-Au NPs greatly enhanced the detection signal. • The immunosensor displayed high specificity and sensitivity for ALV-J detection. [ABSTRACT FROM AUTHOR]

Abstract: We studied the role of organic semiconductor spacer tris (8-hydroxyquinoline) ) in a hybrid spin valve which is comprised of (x 2, TCNE: tetracyanoethylene) and Fe as the ferromagnetic layers. We compare two types of devices: Fe//Al and Fe///Al, showing that organic spacer is not indispensable for the appearance of the spin valve effect. However, the device with spacer has magnetoresistance (MR) value one order of magnitude larger than the device without spacer. The MR of both devices diminish with increasing temperature, while only the Fe//Al device shows room-temperature MR. [Copyright &y& Elsevier]

Abstract: Porous polyaniline (PANI) is prepared by using sodium dodecylsulfate as a soft template and ammonium persulfate as an oxidant. Transmission electron microscopy and nitrogen adsorption–desorption isotherms suggest the existence of both macro/mesopores and micropores, and the specific surface area of 211m2 g−1. As a result of its porous structure, the porous PANI exhibits highly enhanced utilization ratio during the charge–discharge cycles. This porous PANI also displays high cycle stability and rate capability. [Copyright &y& Elsevier]

Background: The cranial region is a complex set of blood vessels, cartilage, nerves and soft tissues. The reconstruction of cranial defects caused by trauma, congenital defects and surgical procedures presents clinical challenges. Our previous data showed that deficiency of the proteoglycan (PG) form of dentin matrix protein 1 (DMP1-PG) could lead to abnormal cranial development. In addition, DMP1-PG was highly expressed in the cranial defect areas. The present study aimed to investigate the potential role of DMP1-PG in intramembranous ossification in cranial defect repair. Methods: Mouse cranial defect models were established by using wild- type (WT) and DMP1-PG point mutation mice. Microcomputed tomography (micro-CT) and histological staining were performed to assess the extent of repair. Immunofluorescence assays and real-time quantitative polymerase chain reaction (RT‒qPCR) were applied to detect the differentially expressed osteogenic markers. RNA sequencing was performed to probe the molecular mechanism of DMP1-PG in regulating defect healing. Results: A delayed healing process and an abnormal osteogenic capacity of primary osteoblasts were observed in DMP1-PG point mutation mice. Furthermore, impaired inflammatory signaling pathways were detected by using RNA transcription analysis of this model. Conclusions: Our data indicate that DMP1-PG is an indispensable positive regulator during cranial defect healing. [ABSTRACT FROM AUTHOR]

Orthodontic tooth movement is a mechanobiological reaction induced by appropriate forces, including bone remodeling. The mechanosensitive Piezo channels have been shown to contribute to bone remodeling. However, information about the pathways through which Piezo channels affects osteoblasts remains limited. Thus, we aimed to investigate the influence of Piezo1 on the osteogenic and osteoclast factors in osteoblasts under mechanical load. Cyclic stretch (CS) experiments on MC3T3-E1 were conducted using a BioDynamic mechanical stretching device. The Piezo1 channel blocker GsMTx4 and the Piezo1 channel agonist Yoda1 were used 12 h before the application of CS. MC3T3-E1 cells were then subjected to 15% CS, and the expression of Piezo1, Piezo2, BMP-2, OCN, Runx2, RANKL, p-p65/p65, and ALP was measured using quantitative real-time polymerase chain reaction, western blot, alkaline phosphatase staining, and immunofluorescence staining. CS of 15% induced the highest expression of Piezo channel and osteoblast factors. Yoda1 significantly increased the CS-upregulated expression of Piezo1 and ALP activity but not Piezo2 and RANKL. GsMTx4 downregulated the CS-upregulated expression of Piezo1, Piezo2, Runx2, OCN, p-65/65, and ALP activity but could not completely reduce CS-upregulated BMP-2. The appropriate force is more suitable for promoting osteogenic differentiation in MC3T3-E1. The Piezo1 channel participates in osteogenic differentiation of osteoblasts through its influence on the expression of osteogenic factors like BMP-2, Runx2, and OCN and is involved in regulating osteoclasts by influencing phosphorylated p65. These results provide a foundation for further exploration of osteoblast function in orthodontic tooth movement. • 15% cyclic stretch is optimal for MC3T3 to express Piezo and osteoblast markers. • Piezo1 and Piezo2 channels were upregulated by cyclic stretch stimuli in MC3T3. • Blocking/activating Piezo1 regulates Piezo2. • Blocking/activating Piezo1 regulates BMP-2, OCN, Runx2, P-P65/P65, ALP activity. [ABSTRACT FROM AUTHOR]

Appropriate design of electrode structure and chemistry for Zn metal anode is important to the kinetics and electrochemical stability of Zn in aqueous batteries. Herein, In modified Zn powder electrode with carbon nanofibers as the stable electric conductive matrix provides an effective approach to simultaneously enhance reaction kinetics and inhibit H 2 generation reactions. The designed Zn–In powder electrode presents self-mixing In distribution within the electrode during cycling thus enabling superior anti-corrasion and stable conductive network that significantly alters the Zn deposition behavior. Instant 3D Zn deposition with super-fast interfacial kinetics is achieved due to favorable Zn nucleation and growth as well as suppressed side reactions. Stable cycling of over 6300 h is achieved, which is 30-fold longer lifespan than Zn foil anode. Even at 5 mA cm−2, 5 mAh cm−2 (depth of discharge: 31.1%), Zn–In powder anode still presents stable cycling of over 500 h and low polarization voltage. Ultra-long cycle life of over 20,000 cycles can be achieved for full cells using Zn–In powder electrode paired with V 2 O 5 cathode. Modified composite Zn powder electrode provides an effective and practical approach to address the electrochemical stability of Zn-based anodes in rechargeable cells. In modified Zn powder electrode with carbon nanofibers as the stable electric conductive matrix (Zn–In@CNFs) provides an effective approach to simultaneously enhance reaction kinetics and inhibit H 2 generation reactions. Zn–In@CNFs powder composite electrode enables self-mixing of In and Zn within the electrode during repeated Zn plating/stripping reactions and induces instant 3D Zn diffusion mode. Modified composite Zn powder electrode provides an effective approach to address the electrochemical stability of Zn-based anodes in rechargeable cells. [Display omitted] • In and carbon nanofiber modified Zn powder electrode regulates the nucleation and growth modes of Zn for enhanced stability. • The modified Zn powder electrode achieves a cooperative suppression of the HER and enhanced reaction kinetics. • Ultra-long life for aqueous Zn–V 2 O 5 full cell is achived with modified Zn powder electrode. [ABSTRACT FROM AUTHOR]

The NSD proteins, namely NSD1, NSD2 and NSD3, are lysine methyltransferases, which catalyze mono- and di-methylation of histone H3K36. They are multi-domain proteins, including two PWWP domains (PWWP1 and PWWP2) separated by some other domains. These proteins act as potent oncoproteins and are implicated in various cancers. However the biological functions of these PWWP domains are still largely unknown. To better understand the functions of these proteins' PWWP domains, we cloned, expressed and purified all the PWWP domains of these NSD proteins to characterize their interactions with methylated histone peptides and dsDNA by quantitative binding assays and crystallographic analysis. Our studies indicate that all these PWWP domains except NSD1_PWWP1 bind to trimethylated H3K36, H3K79 peptides and dsDNA weakly. Our crystal structures uncover that the NDS3_PWWP2 and NSD2_PWWP1 domains, which hold an extremely long α-helix and α-helix bundle, respectively, need a conformation adjustment to interact with nucleosome. • NSD PWWP domains except NSD1_PWWP1 bind to histone H3K36/79me3 and dsDNA weakly. • The NSD3_PWWP2 holds a unique long C-terminal α-helix following the β-barrel. • The NSD2_PWWP1 bears a C-terminal α-helix bundle containing 4 α-helices. • NSD PWWPs interact with methylated histone similar to other reported PWWP domains. • NSD3_PWWP2 and NSD2_PWWP1 need conformational changes to interact with nucleosome. [ABSTRACT FROM AUTHOR]

Rationally designing efficient nanomaterials for heterogeneous activation of peroxymonosulfate (PMS) is necessary for environmental remediation. Nitrogen-containing carbon/FeCo 2 O 4 composites (FeCo 2 O 4 -N-C) were prepared by annealing the iron and cobalt in the ZIF-67 (Fe-Co-ZIF) precursor at different reaction temperatures. In the presence of PMS, 400 °C calcined nitrogen-containing carbon/FeCo 2 O 4 composites (FeCo 2 O 4 -N-C-400) was used as catalyst for heterogeneous Fenton degradation of methylene blue (MB) and nearly 100% MB was removed within 10 min without pH adjustment. FeCo 2 O 4 -N-C-400 had excellent catalytic activity profiting from the uniform distribution of bimetals and nitrogen doping, which ensured the exposure of sites with high catalytic activity. Free radical quenching experiments showed that a large number of reactive oxygen species (SO 4 .- and .OH) were the cause of pollutant degradation. At the same time, the possible degradation mechanism of MB in FeCo 2 O 4 -N-C-400/PMS system was proposed. In addition, FeCo 2 O 4 -N-C-400 can still degrade 60% of MB after four cycles, which indicated that the catalyst had long-term catalytic durability and recyclability. [Display omitted] • The prepared FeCo 2 O 4 -N-C had the characteristics of nitrogen and bimetal doping. • FeCo 2 O 4 -N-C-400 showed a polyhedral morphology with the rougher and looser surface. • FeCo 2 O 4 -N-C can activate PMS to degrade methylene blue without pH adjustment. • Sulfate radicals and hydroxyl participating in Fenton-like process were evidenced. • FeCo 2 O 4 -N-C had long-term catalytic durability and recyclability. [ABSTRACT FROM AUTHOR]

• The glycolysis level is decreased in villi of RSA patients. • The low-level glycolysis of trophoblast cells inhibits M2 polarization of macrophages. • AOC4P is abnormally elevated in villi of RSA patients. • The binding of AOC4P and TRAF6 promotes the degradation of EZH2, thus reducing the glycolysis level of trophoblasts. During embryo implantation, trophoblast cells rely on large amounts of energy produced by glycolysis for their rapid growth and invasion. The disorder of trophoblast metabolism may lead to recurrent spontaneous abortion (RSA). Lactate, which is produced by the glycolysis of trophoblast cells during early pregnancy, can promote the polarization of M2 macrophages and maintain an anti-inflammatory environment at the maternal-fetal interface. Our study found that amine oxidase copper-containing 4 pseudogene (AOC4P) was abnormally increased in villi from RSA patients. It inhibited the glycolysis of trophoblast cells and thus hindered the polarization of M2 macrophages. Further studies showed that AOC4P combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) to upregulate TRAF6 expression. TRAF6 acted as an E3 ubiquitin ligase to promote ubiquitination and degradation of zeste homolog 2 (EZH2). These results provided new insights into the important role played by AOC4P at the maternal-fetal interface. [ABSTRACT FROM AUTHOR]

Oral cancer (OC), characterized by malignant tumors in the mouth, is one of the most prevalent malignancies worldwide. Chemotherapy is a commonly used treatment for OC; however, it often leads to severe side effects on human bodies. In recent years, nanotechnology has emerged as a promising solution for managing OC using nanomaterials and nanoparticles (NPs). Nano-drug delivery systems (nano-DDSs) that employ various NPs as nanocarriers have been extensively developed to enhance current OC therapies by achieving controlled drug release and targeted drug delivery. Through searching and analyzing relevant research literature, it was found that certain nano-DDSs can improve the therapeutic effect of drugs by enhancing drug accumulation in tumor tissues. Furthermore, they can achieve targeted delivery and controlled release of drugs through adjustments in particle size, surface functionalization, and drug encapsulation technology of nano-DDSs. The application of nano-DDSs provides a new tool and strategy for OC therapy, offering personalized treatment options for OC patients by enhancing drug delivery, reducing toxic side effects, and improving therapeutic outcomes. However, the use of nano-DDSs in OC therapy still faces challenges such as toxicity, precise targeting, biodegradability, and satisfying drug-release kinetics. Overall, this review evaluates the potential and limitations of different nano-DDSs in OC therapy, focusing on their components, mechanisms of action, and laboratory therapeutic effects, aiming to provide insights into understanding, designing, and developing more effective and safer nano-DDSs. Future studies should focus on addressing these issues to further advance the application and development of nano-DDSs in OC therapy. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Ethanol consumption has been reported to reduce morbidity in RA patients, but the mechanism behind it remains unclear. Our results showed that Muribaculaceae was predominant in the gut microbiota of mice after ethanol treatment, and the levels of microbiota metabolite acetate were increased. Acetate reduced arthritis severity in collagen-induced arthritis (CIA) mice, which was associated with a decrease in the articular neutrophils and the myeloperoxidase-deoxyribonucleic acid complex in serum. Meanwhile, in vitro experiments confirmed that acetate affected neutrophil activity by acting on G-protein-coupled receptor 43, which reduced endoplasmic reticulum stress in neutrophils and inhibited neutrophil extracellular traps formation. Furthermore, exogenous acetate reversed CIA mice with exacerbated gut microbial disruption, further confirming that the effect of gut microbial metabolite acetate on neutrophils in vivo is crucial for the immune regulation. Our findings illuminate the metabolic and cellular mechanisms of the gut-joint axis in the regulation of autoimmune arthritis, and may offer alternative avenues to replicate or induce the joint-protective benefits of ethanol without associated detrimental effects. Insights into metabolic mechanisms of the gut-joint axis in the regulation of autoimmune arthritis offer alternative avenues to replicate or induce the joint-protective benefits of ethanol without associated detrimental effects. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low‐grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis. Methods: The expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real‐time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/mL to construct the PCOS model. After lentivirus‐infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. Human monocyte cell line (THP‐1)‐derived macrophages and peripheral blood mononuclear cells (PBMC) were co‐cultured with KGN cells for 48 h, respectively, and the differentiation of macrophages and CD4+ T cells were detected by flow cytometry. Results: Decreased AOC4P expression was found in PCOS patients. After constructing the PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co‐culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, T helper cells type 1 (Th1)/Th2 ratio increased, and regulatory T cell (Treg) cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NF‐κB) pathway in KGN cells. Conclusions: In this study, we found that AOC4P regulated the NF‐κB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, thus contributing to the pathogenesis of PCOS. [ABSTRACT FROM AUTHOR]

RBBP1 is a retinoblastoma protein (pRb) binding protein acting as a repressor of gene transcription. RBBP1 is a multidomain protein including a chromo barrel domain, and its chromo barrel domain has been reported to recognize histone H4K20me3 weakly, and this binding is enhanced by the simultaneous binding of DNA. However, the molecular basis of this DNA-mediated histone binding by the chromo barrel domain of RBBP1 is unclear. Here we attempted to co-crystallize the chromo barrel domain of RBBP1 with either a histone H4K20me3 peptide alone or with both a histone H4K20me3 peptide and DNA, but only solved the peptide/DNA unbound crystal structure. Our structural analysis indicates that RBBP1 could interact with histone H4K20me3 similar to other histone binding chromo barrel domains, and the surface charge representation analysis of the chromo barrel domain of RBBP1 suggests that the chromo barrel domain of RBBP1 does not have a typical DNA binding surface, indicating that it might not bind to DNA. Consistently, our ITC assays also showed that DNA does not significantly enhance the histone binding ability of the chromo barrel domain of RBBP1. [ABSTRACT FROM AUTHOR]

Introduction: As effective interventions to prevent inpatient falls are lacking, a novel technological intervention was trialed. The Ambient Intelligent Geriatric Management (AmbIGeM) system used wearable sensors that detected and alerted staff of patient movements requiring supervision. While the system did not reduce falls rate, it is important to evaluate the acceptability, usability, and safety of the AmbIGeM system, from the perspectives of patients and informal carers. Methods: We conducted a mixed-methods study using semistructured interviews, a pre-survey and post-survey. The AmbIGeM clinical trial was conducted in two geriatric evaluation and management units and a general medical ward, in two Australian hospitals, and a subset of participants were recruited. Within 3 days of being admitted to the study wards and enrolling in the trial, 31 participants completed the pre-survey. Prior to discharge (post-intervention), 30 participants completed the post-survey and 27 participants were interviewed. Interview data were thematically analyzed and survey data were descriptively analyzed. Results: Survey and interview participants had an average age of 83 (SD 9) years, 65% were female, and 41% were admitted with a fall. Participants considered the AmbIGeM system a good idea. Most but not all thought the singlet and sensor component as acceptable and comfortable, with no privacy concerns. Participants felt reassured with extra monitoring, although sometimes misunderstood the purpose of AmbIGeM as detecting patient falls. Participants' acceptability was strongly positive, with median 8+ (0–10 scale) on pre- and post-surveys. Discussion/Conclusion: Patients' acceptability is important to optimize outcomes. Overall older patients considered the AmbIGeM system as acceptable, usable, and improving safety. The findings will be important to guide refinement of this and other similar technology developments. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the regulation of the miR-410-5p /ITGA6 axis on the biological functions of trophoblast cells and the mechanism involved in recurrent spontaneous abortion（RSA）. We used qRT-PCR and Western blotting to quantify the expression levels of Mir-410-5p and ITGA6 in placenta of RSA and normal, and found that compared with normal placenta, the placenta of RSA patients showed higher miR-410-5p and lower ITGA6 expression. Dual luciferase reporter gene assay confirmed the binding of miR-410-5p to ITGA6. The expression of miR-410-5p and ITGA6, and proliferation, apoptosis, invasion and migration of trophoblast cells and the effect on the polarization of M2 macrophages were detected in the trophoblast derived cell lines HTR8/Svneo transfected with miR-410-5p mimic, sh-miR-410-5p and si-ITGA6 respectively. Meanwhile, the molecular mechanism of ITGA6 regulation on trophoblast cells was explored. Transfection with miR-410-5p mimic or si-ITGA6 attenuated the proliferation, migration and invasion and induced apoptosis of HTR-8/SVneo cells. Transfection of sh-miR-410-5p promoted proliferation, migration and invasion, and weakened apoptosis of HTR-8/SVneo cells. In addition, overexpression of miR-410-5p in trophoblast cells inhibited the polarization of M2 macrophages, while knockdown of miR-410-5p was beneficial to recruitment of trophoblast cell and promoted the polarization of M2 macrophages. ITGA6 may affect the biological functions of trophoblast cells by regulating PI3K/AKT and MAPK signaling pathways. In conclusion, miR-410-5p mediates trophoblast cell proliferation, apoptosis, invasion and migration through regulating ITGA6 expression. • The expression of miR-410-5p was increased while the expression of ITGA6 was decreased in villi of RSA patients. • MiR-410-5p regulated the proliferation and invasion of trophoblast cells and affected the polarization of M2 macrophages. • ITGA6 might affect the function of trophoblast cells by regulating PI3K/AKT and MAPK pathways. [ABSTRACT FROM AUTHOR]

Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental follicle progenitor cells (DFPCs), which are stem cells found in dental follicles, differentiate into different kinds of cells that are necessary for tooth formation and eruption. Runt‐related transcription factor 2 (Runx2) is a transcription factor that is essential for osteoblasts and osteoclasts differentiation, as well as bone remodeling. Mutation of Runx2 causing cleidocranial dysplasia negatively affects osteogenesis and the osteoclastic ability of dental follicles, resulting in tooth eruption difficulties. Among a variety of cells and molecules, Nel-like molecule type 1 (Nell-1) plays an important role in neural crest-derived tissues and is strongly expressed in dental follicles. Nell-1 was originally identified in pathologically fused and fusing sutures of patients with unilateral coronal synostosis, and it plays indispensable roles in bone remodeling, including roles in osteoblast differentiation, bone formation and regeneration, craniofacial skeleton development, and the differentiation of many kinds of stem cells. Runx2 was proven to directly target the Nell-1 gene and regulate its expression. These studies suggested that Runx2/Nell-1 axis may play an important role in the process of tooth eruption by affecting DFPCs. Studies on short and long regulatory noncoding RNAs have revealed the complexity of RNA-mediated regulation of gene expression at the posttranscriptional level. This ceRNA network participates in the regulation of Runx2 and Nell-1 gene expression in a complex way. However, non-study indicated the potential connection between Runx2 and Nell-1, and further researches are still needed. [ABSTRACT FROM AUTHOR]

[Display omitted] • DNA binding abilities of Arabidopsis thaliana MBD proteins have been characterized systematically. • AtMBD6 and AtMBD7 serve as the methylated DNA "readers". • Crystal structures of AtMBD6-mCG and apo-state AtMBD5 MBD were determined. • The arginine fingers coupled with the loop1 and α1 of MBD contribute to DNA binding. • This study provides general guidelines in understanding the DNA binding by MBD. 13 MBD-containing genes (AtMBD1-13) have been identified in Arabidopsis thaliana so far, however, their DNA binding ability is still controversial. Here, we systematically measured the DNA binding affinities of these MBDs by ITC and EMSA binding assays, except for those of pseudogenes AtMBD3 and AtMBD13, and found that only AtMBD6 and AtMBD7 function as methylated DNA readers. We also found that the MBD of AtMBD5 exhibits very weak binding to methylated DNA compared to that of AtMBD6. To further investigate the structural basis of AtMBDs in binding to methylated DNA, we determined the complex structure of the AtMBD6 MBD with a 12mer mCG DNA and the apo structure of the AtMBD5 MBD. Structural analysis coupled with mutagenesis studies indicated that, in addition to the conserved arginine fingers contributing to the DNA binding specificity, the residues located in the loop1 and α1 are also essential for the methylated DNA binding of these MBDs in Arabidopsis thaliana , which explains why AtMBD5 MBD and the other AtMBDs display very weak or no binding to methylated DNA. Thus, our study here systematically demonstrates the DNA binding ability of the MBDs in Arabidopsis thaliana , which also provides a general guideline in understanding the DNA binding ability of the MBDs in other plants as a whole. [ABSTRACT FROM AUTHOR]

As a means of communication between immune cells and non-immune cells, Interleukins (ILs) has the main functions of stimulating the proliferation and activation of inflammatory immune cells such as dendritic cells and lymphocytes, promote the development of blood cells and so on. However, dysregulation of ILs expression is a major feature of autoinflammatory diseases. The drugs targeting ILs or IL-like biologics have played an important role in the clinical treatment of autoinflammatory diseases. Nevertheless, the widespread use of IL products may result in significant off-target adverse reactions. Thus, there is a clear need to develop next-generation ILs products in the biomedical field. Fusion proteins are proteins created through the joining of two or more genes that originally coded for separate proteins. Over the last 30 years, there has been increasing interest in the use of fusion protein technology for developing anti-inflammatory drugs. In comparison to single-target drugs, fusion proteins, as multiple targets drugs, have the ability to enhance the cytokine therapeutic index, resulting in improved efficacy over classical drugs. The strategy of preparing ILs or their receptors as fusion proteins is increasingly used in the treatment of autoimmune and chronic inflammation. This review focuses on the efficacy of several fusion protein drugs developed with ILs or their receptors in the treatment of autoinflammatory diseases, in order to illustrate the prospects of this new technology as an anti-inflammatory drug development protocol in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

A Mach-Zehnder interferometer for measurement of temperature is proposed and experimentally demonstrated, which consists of two sections of single mode fiber (SMF) and a section of thin core fiber spliced between the two SMFs. The two welding areas are heated and stretched to improve the split and recombination of light. The wavelength of the resonant dip will shift when temperature varies due to the thermo-optic and thermal expansion effect. The experimental results show that a temperature sensitivity of 65 pm/°C with a linear correlation coefficient of 0.996 can be achieved in a temperature range from 25 °C to 80 °C. Due to its ease of manufacture, low cost, and high sensitivity, the fiber optic temperature sensor is suitable for temperature measurement applications. [ABSTRACT FROM AUTHOR]

Alfin1-like (AL) is a family of proteins homologous to the alfalfa Alfin1 in plant and bears an Alfin domain and a PHD domain at their N- and C-terminus, respectively. There are 7 AL proteins in Arabidopsis, and the PHD domains of most AL proteins are reported to bind to histone H3K4me3. Here we reported gene cloning, protein expression and purification of the PHD domains of all the AL family proteins in Arabidopsis. We then systematically characterized their histone binding abilities by quantitative isothermal titration calorimetry and fluorescence polarization binding assays. Our binding results indicate that all the PHD domains of the AL proteins bind to the histone H3K4me3 peptide with varying methylation state preference and binding affinities. Our study presented here provides the foundation for further studies of the peptide state-specific recognition by PHD domains of AL proteins. [ABSTRACT FROM AUTHOR]

Nanoflower-like architectures represent a unique type of nanomaterials in which thin 2D nanosheets are self-organised into interconnected structures. Lack of restacking between nanosheets and significant internal porosity are the particular advantages of such nanoscale architectures. A general method for the preparation of nanoflowers of a range of oxides (e.g., FeTiO3, TiO2, Mn2O3) through a two-step procedure of ball milling and subsequent hydrothermal treatment is outlined. Importantly, the synthetic method is valid not only for a single oxide, but is extendable to a family of oxide materials. It is established that the formation of the nanoflowers from ball-milled powders follows a dissolution-precipitation mechanism; this is confirmed by inductively coupled plasma time of flight mass spectrometry measurements. Additional information on the X-ray photoelectron spectroscopy characterisation and intermediate stage of growth of the nanostructures is included. Furthermore, two applications of Mn2O3 nanostructures are briefly investigated. Firstly, their properties for energy storage in the electrodes of electrochemical supercapacitors are presented. A capacitive response in the potential window of -0.1-0.9 V versus an Ag/AgCl reference electrode is observed, with an associated increase of the capacitance values over cycling. Secondly, the use of Mn2O3 nanoflowers as model systems for the development of novel nanofabrication techniques (such as nanopatterning with a He+ beam) is investigated. [ABSTRACT FROM AUTHOR]

Abstract: The fabrication conditions of Cu–Al–Ni–Mn alloy powder by mechanical alloying and powder metallurgy have been systematically studied. The mechanically alloyed powder (MAed powder) was fabricated at a speed between 100rpm and 300rpm for various milling times with and without process control agent (PCA). With an increasing of milling time, the size of crystallite grain decreases. Only the Cu diffraction pattern appear as the rotation speed is up to 300rpm for 25h. The elemental powders with PCA agglomerate slightly, but the degree of alloying is lower than that without PCA. The shape memory recovery of the quenched sample hot-extruded at extrusion rate of 50:1 is measured to be 100% recovered in 250°C oil bath for 40s after deformed to 4.0%. After aging at 120°C for 10 days, the shape memory recovery of the alloy remains 98%. [Copyright &y& Elsevier]