Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity.

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.

Dynamic Transformation of High-Architectural Nanocrystal Superlattices upon Solvent Molecule Exposure.

The cluster-based body-centered-cubic superlattice (cBCC SL) represents one of the most complicated structures among reported nanocrystal assemblies, comprised of 72 truncated tetrahedral quantum dots per unit cell. Our previous report revealed that truncated tetrahedral quantum dots within cBCC SLs possessed highly controlled translational and orientational order owing to an unusual energetic landscape based on the balancing of entropic and enthalpic contributions during the assembly process. However, the cBCC SL's structural transformability and mechanical properties, uniquely originating from such complicated nanostructures, have yet to be investigated. Herein, we report that cBCC SLs can undergo dynamic transformation to face-centered-cubic SLs in response to post-assembly molecular exposure. We monitored the dynamic transformation process using in situ synchrotron-based small-angle X-ray scattering, revealing a dynamic transformation involving multiple steps underpinned by interactions between incoming molecules and TTQDs' surface ligands. Furthermore, our mechanistic study demonstrated that the precise configuration of TTQDs' ligand molecules in cBCC SLs was key to their high structural transformability and unique jelly-like soft mechanical properties. While ligand molecular configurations in nanocrystal SLs are often considered minor features, our findings emphasize their significance in controlling weak van der Waals interactions between nanocrystals within assembled SLs, leading to previously unremarked superstructural transformability and unique mechanical properties. Our findings promote a facile route toward further creation of soft materials, nanorobotics, and out-of-equilibrium assemblies based on nanocrystal building blocks.

Small graft size and hepatocellular carcinoma outcomes in living donor liver transplantation: a retrospective multicentric cohort study.

INTRODUCTION: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and HCC outcomes. MATERIALS AND METHODS: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014-2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR<0.7% vs. GRWR≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. RESULTS: The eligible cohort consisted of 2005 LDLT recipients (GRWR<0.7 [n=59] vs. GRWR≥0.7 [n=1946]). In the entire cohort, 5-year RFS was significantly lower in the GRWR<0.7 than in the GRWR≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR<0.7 was an independent risk factor for RFS (adjusted HR [aHR] 1.89, P =0.012), but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR<0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). CONCLUSIONS: A GRWR<0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.

Unlocking the Metalation Applications of TMP-powered Fe and Co(II) bis(amides): Synthesis, Structure and Mechanistic Insights.

Typified by LiTMP and TMPMgCl.LiCl, (TMP=2,2,6,6-tetramethylpiperidide), s-block metal amides have found widespread applications in arene deprotonative metalation. On the contrary, transition metal amides lack sufficient basicity to activate these substrates. Breaking new ground in this field, here we present the synthesis and full characterisation of earth-abundant transition metals M(TMP)2 (M=Fe, Co). Uncovering a new reactivity profile towards fluoroarenes, these amide complexes can promote direct M-H exchange processes regioselectively using one or two of their basic amide arms. Remarkably, even when using a perfluorinated substrate, selective C-H metalation occurs leaving C-F bonds intact. Their kinetic basicity can be boosted by LiCl or NBu4Cl additives which enables formation of kinetically activated ate species. Combining spectroscopic and structural studies with DFT calculations, mechanistic insights have been gained on how these low polarity metalation processes take place. M(TMP)2 can also be used to access ferrocene and cobaltocene by direct deprotonation of cyclopentadiene and undergo efficient CO2 insertion of both amide groups under mild reaction conditions.

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

In vitro metabolism of the emerging contaminant 6PPD-quinone in human and rat liver microsomes: Kinetics, pathways, and mechanism.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is an ozonation product of the rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD). 6PPD-Q has recently been detected in various environmental media, which may enter the human body via inhalation and skin contact pathways. However, the human metabolism of 6PPD-Q has remained unknown. This study investigated the in vitro Cytochrome P450-mediated metabolism of 6PPD-Q in human and rat liver microsomes (HLMs and RLMs). 6PPD-Q was significantly metabolized at lower concentrations but slowed at high concentrations. The intrinsic clearance (CLint) of 6PPD-Q was 21.10 and 18.58 µL min-1 mg-1 protein of HLMs and RLMs, respectively, suggesting low metabolic ability compared with other reported pollutants. Seven metabolites and one intermediate were identified, and metabolites were predicted immunotoxic or mutagenic toxicity. Mono- and di-oxygenation reactions were the main phase I in vitro metabolic pathways. Enzyme inhibition experiments and molecular docking techniques were further used to reveal the metabolic mechanism. CYP1A2, 3A4, and 2C19, especially CYP1A2, play critical roles in 6PPD-Q metabolism in HLMs, whereas 6PPD-Q is extensively metabolized in RLMs. Our study is the first to demonstrate the in vitro metabolic profile of 6PPD-Q in HLMs and RLMs. The results will significantly contribute to future human health management targeting the emerging pollutant 6PPD-Q.

Real-world data of China: Analysis of HPV vaccine coverage and post-vaccination adverse reaction monitoring in Western Chinese provinces from 2018 to 2021.

To investigate the HPV vaccine coverage and post-vaccination adverse reactions in Gansu Province, Western China, from 2018 to 2021. Data on suspected adverse reactions to HPV vaccines were collected from the Chinese Vaccine Adverse Event Following Immunization (AEFI). Estimate the incidence rates of Common Adverse Reaction and Rare Adverse Reaction. HPV vaccine coverage among females in different age groups was calculated using data from the Gansu Provincial Immunization Information Platform. The first-dose HPV vaccine coverage rate among females aged 9 to 45 was 2.02%, with the lowest rate of less than 1% observed in females aged 9 to 14. From 2018 to 2021, the incidence rates of Common Adverse Reaction and Rare Adverse Reaction reported in females after HPV vaccination were 11.82 and 0.39 per 100,000 doses, respectively. Common Adverse Reaction included fever (5.52 per 100,000 doses), local redness and swelling (3.33 per 100,000 doses), fatigue (3.15 per 100,000 doses), headache (2.76 per 100,000 doses), as well as local induration and nausea/vomiting (1.97 per 100,000 doses). Adverse reactions mainly occurred within 1 day after vaccination, followed by 1 to 3 days after vaccination. The HPV vaccine coverage rate among females aged 9 to 14 in Gansu Province is remarkably low, and there is an urgent need to enhance vaccine coverage. From 2018 to 2021, the incidence of Adverse reaction Following Immunization HPV vaccination fell within the expected range, indicating the vaccine's safety profile.

Visible light-promoted difluoromethylthiolation of cycloalkanols by C-C bond cleavage.

A mild and general methodology for the difluoromethylthiolation of cycloalkanols has been developed by employing N-difluoromethylthiophthalimide as the SCF2H radical source, in combination with an acridinium-derived organo-photosensitizer, under redox-neutral conditions. This reaction protocol demonstrates high efficiency, scalability, and mild reaction conditions, thus presenting a green approach for the rapid synthesis of distal difluoromethylthiolated alkyl ketones that are challenging to be synthesized through alternative means.

Ni clusters immobilized on oxygen-rich siloxene nanosheets for efficient electrocatalytic oxygen reduction toward H2O2 synthesis.

Hydrogen peroxide (H2O2) electrosynthesis via the two-electron oxygen reduction reaction (2e- ORR) represents a green alternative to the energy-intensive anthraquinone process. However, the practical application of this method is limited by the lack of cost-effective and high-performance electrocatalysts. Reported here is a hybrid catalyst composed of nickel (Ni) clusters immobilized onto the surface of two-dimensional siloxene nanosheets (Ni/siloxene), which exhibits excellent efficiency and selectivity in electrocatalytic oxygen reduction to H2O2 in an alkaline medium, demonstrating a standard 2e- pathway with >95% H2O2 selectivity across a wide potential range. Experimental results disclose that the high performance of Ni/siloxene can be traced to a synergy of the Ni clusters and the oxygen-rich surface of siloxene. Density functional theory (DFT) calculations further reveal a weakened interaction between Ni/siloxene and *OOH and the consequently reduced energy barrier for the *OOH protonation toward H2O2 desorption, thus leading to a high 2e- ORR reactivity and selectivity. This work provides a valuable and practical guidance for designing high-performance 2e- ORR electrocatalysts based on the rational engineering of the metal-support interaction.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

Ferroptosis heterogeneity within the tumor microenvironment revealed a genetic blueprint of breast cancer.

The tumor microenvironment (TME) significantly influences disease progression through immune infiltration, while ferroptosis, a recently discovered cell death mechanism, plays a crucial role in tumor suppression. However, its role in breast cancer is not clear. In this study, we analyzed bulk RNA and single-cell RNA sequencing data from 1217 samples, including 1104 breast cancer patients and 113 controls, to identify ferroptosis-related genes (FRGs) and construct a prognostic model. Using univariate cox regression, LASSO regression, and multivariate cox regression analysis, we discovered 21 FRGs and 3 TME-related immune cell types with prognostic value. Dimensionality reduction clustering and visualization were performed using the UMAP method, while the immune infiltration process was calculated with the TIP online tool. We employed GSEA enrichment analysis, WGCNA clustering analysis, and correlation analysis to examine functional differences, and the mutation analysis of the best and worst prognosis groups was conducted using the maftools package. Our findings revealed that knocking down the expression of the hub gene SLC39A7 significantly impacted cancer cell apoptosis and combining ferroptosis and TME scores yielded high prognostic power. Epithelial cells and B cells exhibited higher ferroptosis scores, which were independently associated with immune checkpoint blockade (ICB) response and ICB gene expression. This study provides a foundation for further exploration of the relationship between ferroptosis and ICB response in breast cancer. In conclusion, we developed a prognostic model based on ferroptosis and infiltrated immune cells that effectively stratified breast cancer patients and demonstrated the role of SLC39A7 in breast cancer pathogenesis through the regulation of apoptosis.

PIEZO2 expression is an independent biomarker prognostic for gastric cancer and represents a potential therapeutic target.

Gastric cancer (GC) is one of the most prevalent malignant tumors of the gastrointestinal system in the globe. The effect of PIEZO2 on the immune function and pathological features of gastric cancer remains to be explored. The Online database of cancer genes and GSE54129 have been used to analyze the clinical characteristics of PIEZO2 expression. We looked at the relationship between PIEZO2 and the immune systems of GC patients. The TIDE algorithm was used to explore the value of PIEZO2 in immunotherapy. Investigated the enrichment of PIEZO2 gene ontology and associated signal pathways using Online gene databases. The results show that overexpression of PIEZO2 was identified as an independent risk factor for patients with GC who had poor overall survival. Individuals may have a better prognosis if they had poorly differentiated GC and increased PIEZO2 expression (P < 0.05). We demonstrated a strong correlation between PIEZO2 and immune cells. The majority of immune checkpoint and immunological-related genes were associated with PIEZO2 expression. And PIEZO2 might be used as an immunotherapy target. Finally, the differential PIEZO2 genes in GC were mostly implicated in the processes of inflammation, immunological response, and tumor metastasis, according to functional analysis. PIEZO2 has a negative correlation with cell stemness and mutation levels in patients with GC and a positive correlation with immune cell infiltration and gene expression in the tumor microenvironment. These findings point to PIEZO2 as a potential new immunotherapy target of GC.

Lanthanide Doping into All-Inorganic Heterometallic Halide Layered Double Perovskite Nanocrystals for Multimodal Visible and Near-Infrared Emission.

The introduction of lanthanide ions (Ln3+) into all-inorganic lead-free halide perovskites has captured significant attention in optoelectronic applications. However, doping Ln3+ ions into heterometallic halide layered double perovskite (LDP) nanocrystals (NCs) and their associated doping mechanisms remain unexplored. Herein, we report the first colloidal synthesis of Ln3+ (Yb3+, Er3+)-doped LDP NCs utilizing a modified hot-injection method. The resulting NCs exhibit efficient near-infrared (NIR) photoluminescence in both NIR-I and NIR-II regions, achieved through energy transfer down-conversion mechanisms. Density functional theory calculations reveal that Ln3+ dopants preferentially occupy the Sb3+ cation positions, resulting in a disruption of local site symmetry of the LDP lattices. By leveraging sensitizations of intermediate energy levels, we delved into a series of Ln3+-doped Cs4M(II)Sb2Cl12 (M(II): Cd2+ or Mn2+) LDP NCs via co-doping strategies. Remarkably, we observe a brightening effect of the predark states of Er3+ dopant in the Er3+-doped Cs4M(II)Sb2Cl12 LDP NCs owing to the Mn component acting as an intermediate energy bridge. This study not only advances our understanding of energy transfer mechanisms in doped NCs but also propels all-inorganic LDP NCs for a wider range of optoelectronic applications.

Exploring the causal association of rheumatoid arthritis with atrial fibrillation: a Mendelian randomization study.

BACKGROUND: It has been proved that rheumatoid arthritis (RA) patients have high incidence of atrial fibrillation (AF). Nevertheless, whether they have causal relevance is uncertain. This study aimed to explore and verify the authenticity of causal relationship between RA and AF using Mendelian randomization (MR). METHODS: The genome-wide association study (GWAS) summary data from Biobank Japan Project (BBJ) (RA, 4199 cases and 208,254 controls) were regarded as exposure data and the GWAS data from European Bio-informatics Institute database (EBI) (AF, 15,979 cases and 102,776 controls) as outcome data. The causal effect was appraised by the inverse variance weighted (IVW) method, MR-Egger regression, and weighted median estimator. MR-robust adjusted profile score (MR-RAPS) method was delivered to examine the robustness of causal relationship and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) method to control horizontal (directional) pleiotropy. RESULTS: The results indicated that RA increased the risk of AF (IVW, the odds ratio (OR) = 1.060; 95% confidence interval (CI), 1.028 to 1.092; p = 1.411 × 10-4; weighted median, OR = 1.046, 95% CI, 1.002 to 1.093, p = 0.047). The MR analysis also showed this causal effect through all four IVW methods with various statistical algorithms. Both MR-RAPS and MR-PRESSO supported the causality of RA and AF. Also, the MR-PRESSO result indicated the absence of apparent pleiotropy. CONCLUSION: There is a causal association between RA and AF. RA patients are genetically more vulnerable to AF. This study may contribute to further exploring early clinical prevention and fundamental mechanism of AF in patients with RA. Key Points • We provided some genetic evidence for the causal link between rheumatoid arthritis (RA) and atrial fibrillation (AF) with multiple Mendelian randomization (MR) methods. • RA patients were genetically more vulnerable to AF. • This study partly shed light on latent fundamental mechanisms underlying RA-induced AF and inspired future studies on RA-AF relationship.

Generalized machine learning based on multi-omics data to profile the effect of ferroptosis pathway on prognosis and immunotherapy response in patients with bladder cancer.

INTRODUCTION: Bladder cancer (BLCA) affects millions of people worldwide, with high rates of incidence and mortality. Ferroptosis proves to be a novel form of cell death process that is triggered by oxidative stress. METHODS: We procured a total of 25 single nuclear RNA-seq (snRNA-seq) samples from GSE169379 in GEO database. We obtained different cohorts of BLCA patients from the TCGA and GEO databases for model training and validation. A total of 369 ferroptosis-related genes (FRGs) were selected from the FerrDb database. AUCell analysis was performed to assign ferroptosis scores to all the cell types. Weighted Gene Co-Expression Network Analysis (WGCNA), COX, and LASSO regression analysis were conducted to retain and finalize the genes of prognostic values. Various bioinformatic approaches were utilized to depict immune infiltration profile. We conducted a series of colony formation analysis, flow cytometry and western blot (WB) analysis to determine the role of SKAP1 in BLCA. RESULTS: We divided the cells into high ferroptosis group and low ferroptosis group according to ferroptosis activity score, and then screened 2150 genes most associated with ferroptosis by differential expression analysis, which are related to UV-induced DNA damage, male hormone response, fatty acid metabolism and hypoxia. Subsequently, WGCNA algorithm further screened 741 ferroptosis related genes from the 2150 genes for the construction of prognostic model. Lasso-Cox regression analysis was used to construct the prognostic model, and the prognostic model consisting of 6 genes was obtained, namely JUN, SYT1, MAP3K8, GALNT14, TCIRG1, and SKAP1. Next, we constructed a nomogram model that integrated clinical factors to improving the accuracy. In addition, we performed drug sensitivity analyses in different subgroups and found that Staurosporine, Rapamycin, Gemcitabine, and BI-2536 may be candidates for the drugs treatment in high-risk populations. The ESTIMATE results showed higher stromal scores, immune scores, and ESTIMATE scores in the low-risk group, indicating a higher overall immunity level and immunogenicity of tumor microenvironment (TME) in this group, and tumor immune dysfunction and exclusion (TIDE) analysis confirmed a better response to immunotherapy in the low-risk group. Finally, we selected the oncogene SKAP1 in the prognostic gene for in vitro validation, and found that SKAP1 directly regulated BLCA cell proliferation and apoptosis. CONCLUSION: We identified a set of six genes, JUN, SYT1, MAP3K8, GALNT14, TCIRG1, and SKAP1, that exhibited significant potential in stratification of BLCA patients with varying prognosis. In addition, we uncovered the direct regulatory effect of SKAP1 on BLCA cell proliferation and apoptosis, shedding some light on the role of FRGs in pathogenesis of BLCA.

Accidental ABO-incompatible pediatric liver transplantation with blood group antigen immune and operational tolerance: a case report with 21 years of follow-up.

Liver transplantation is a critical procedure for patients with end-stage liver disease, but it is often hindered by ABO-incompatibility between the donor and recipient, which can lead to immediate humoral rejection. We present a unique case involving a 10-month-old patient who, by accident, received an ABO-incompatible partial liver transplant from a type A mother without undergoing desensitization. Remarkably, during a 21-year follow-up period, the patient exhibited no signs of humoral or graft rejection, despite nonadherence to medication. This case highlights the possibility of dual tolerance in pediatric ABO-incompatible liver transplantation and provides insights into immune tolerance mechanisms, with implications for enhancing patient care and reducing healthcare costs. Further research is necessary to clarify these mechanisms and to evaluate the long-term durability of tolerance in pediatric transplant recipients.

Associations between maternal stressful life events experiences and risk of neural tube defects in offspring: a systematic review and meta-analysis.

OBJECTIVES: Multiple factors associated with neural tube defects (NTDs) risk have been identified, yet there is little evidence on the possible effects of maternal stressful life events. In this study, we aimed to investigate the association between stressful life events during the periconceptional period and risk of NTDs in offspring. METHODS: Relevant literature was searched in PubMed, Springer Link, ScienceDirect, and Cochrane Library up to July 2023. The pooled odds ratio (OR) and 95% confidence interval (CI) of NTDs risk with maternal stressful life events were estimated using a random effects model. Publication bias was assessed using Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. RESULTS: Analysis results showed that mothers who experienced stressful life events during the periconceptional period were at greater risk of having NTDs offspring (OR: 1.37, 95% CI: 1.08-1.73) than those who did not. In subgroup analysis, the pooled OR was 1.37 (1.13-1.67) and 1.73 (0.36-8.32) for with and without adjusting for folic acid supplementation in each included study, while was 1.37 (1.13-1.67) and 1.64 (0.39-6.88) for exposure time of three months preconception until three months post conception and one year preconception until three months post conception, respectively. CONCLUSIONS: This study suggests that maternal stressful life events during the periconceptional period are significantly associated with higher NTDs risk in offspring. Tailored approaches for evaluating the risk and policy of NTDs among women of childbearing age should emphasize individual stressful experiences before and during early pregnancy.

Plum-blossom needle therapy for Tourette syndrome: A case report.

INTRODUCTION: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the childhood onset of motor and phonic tics, frequently accompanied by behavioral and psychiatric comorbidities. Existing treatments for tics raise safety concerns. In China, acupuncture has been a widely utilized approach for TS, and one specific traditional acupuncture method, plum-blossom needle therapy (PBNT), has exhibited favorable tolerance among pediatric patients. In this report, we present a case of TS treated using PBNT. CASE PRESENTATION: An 11-year-old boy diagnosed with Tourette syndrome for over five years presented with frequent loud throat clearing, eye blinking, severe abdominal tensing, shoulder shrugging, and upper limb twitching. Plum-blossom needle therapy (PBNT) was administered for 8 weeks, involving two sessions per week. The boy's tic symptoms gradually ameliorated, ultimately becoming minimal following the 8-week treatment period. Specifically, the Yale Global Tic Severity Scale (YGTSS) score decreased from 71 to 20, and the TS Clinical Global Impression Scale of Improvement (CGI-I) score reached 1, signifying 'very much improved' post-treatment. However, the Children and Adolescents' Quality of Life Scale (CAQOL) score exhibited minimal variation, moving from 146 to 150. CONCLUSION: This case suggests that plum-blossom needle therapy (PBNT) is well-tolerated by children and may be effective in alleviating tics associated with Tourette syndrome (TS). However, further research, particularly large-sample randomized controlled trials, is imperative to establish the efficacy and effectiveness of PBNT.

Advances on Axial Coordination Design of Single-Atom Catalysts for Energy Electrocatalysis: A Review.

Single-atom catalysts (SACs) have garnered increasingly growing attention in renewable energy scenarios, especially in electrocatalysis due to their unique high efficiency of atom utilization and flexible electronic structure adjustability. The intensive efforts towards the rational design and synthesis of SACs with versatile local configurations have significantly accelerated the development of efficient and sustainable electrocatalysts for a wide range of electrochemical applications. As an emergent coordination avenue, intentionally breaking the planar symmetry of SACs by adding ligands in the axial direction of metal single atoms offers a novel approach for the tuning of both geometric and electronic structures, thereby enhancing electrocatalytic performance at active sites. In this review, we briefly outline the burgeoning research topic of axially coordinated SACs and provide a comprehensive summary of the recent advances in their synthetic strategies and electrocatalytic applications. Besides, the challenges and outlooks in this research field have also been emphasized. The present review provides an in-depth and comprehensive understanding of the axial coordination design of SACs, which could bring new perspectives and solutions for fine regulation of the electronic structures of SACs catering to high-performing energy electrocatalysis.

Proper position of single and large (≥5 cm) hepatocellular carcinoma in Barcelona Clinic Liver Cancer classification.

The purpose of this study was to evaluate the proper position of single large hepatocellular carcinoma (HCC) in the Barcelona Clinic Liver Cancer (BCLC) staging system. The data were collected from the nationwide multicentre database of the Korean Liver Cancer Association. Patients with single large (≥5 cm) HCC were separated from BCLC stage A patients and designated as Group X. The remaining BCLC stage A and stage B patients were classified as Group A and Group B, respectively. The survival outcomes of propensity score-matched groups were compared. Among the 3965 randomly selected patients, the number of patients in Group X, Group A, and Group B was 414, 2787, and 760, respectively. TriMatch analysis allowed us to obtain 116 well-balanced triplets. The 1-, 3-, and 5-year overall survival rates in Group X were worse than in Group A (91%, 71%, and 48% vs 90%, 78%, and 64%, respectively; P < .000). However, the rates were not different compared with those in Group B (91%, 71%, and 48% vs 90%, 69%, and 48%, respectively; P < .09). In multivariate analysis, Group X, Group B, age over 60 years, prothrombin time-international normalized ratio, and creatinine level were independent predictors of worse overall survival. Our findings suggest that Group X should be relocated to BCLC stage B rather than BCLC stage A.