Negative association between Body Roundness Index and bone mineral density: insights from NHANES.

Background: Osteoporosis (OP), affecting millions around the globe, is a prevalent degenerative condition of the bones characterized by a decrease in bone mineral density (BMD) and an increase in bone fragility. A novel anthropometric measure, the Body Roundness Index (BRI), provides a more accurate assessment of body fat distribution compared to traditional metrics. Using data from the National Health and Nutrition Examination Survey (NHANES), this study aims to explore the relationship between BRI and total BMD in U.S. adults aged 20 and above. Methods: Data from NHANES (2011-2018) were examined, encompassing 9,295 participants following exclusions. Dual-energy X-ray absorptiometry (DXA) was employed to measure BMD. BRI was calculated using waist circumference (WC) and height. The study accounted for variables such as demographic traits, physical exam results, lab test findings, and survey responses. Weighted multivariable linear regression models and smooth curve fitting methods were utilized to assess the relationship between BRI and total BMD. Results: The research found a notable inverse relationship between BRI and total BMD. In the model with full adjustments, an increase of one unit in BRI was linked to a 0.0313 g/cm2 reduction in total BMD (P < 0.0001). Moreover, an inflection point was identified at BRI = 9.5229, where each one-unit rise in BRI beyond this threshold corresponded to a more substantial decrease in total BMD (0.0363 g/cm2). Analysis by subgroups revealed that this negative association was consistent across most demographic and health-related categories. Conclusions: The results demonstrate a notable inverse relationship between BRI and total BMD, indicating that a higher BRI could be associated with lower BMD and a potentially greater risk of developing OP. This underscores the significance of accounting for body fat distribution in preventing OP and advocates for the use of BRI as a valuable marker for early intervention approaches.

One-step Synthesis of Chiral 9,10-Dihydrophenanthrenes via Ligand-enabled Enantioselective Cascade ß,γ-Diarylation of Acids.

Pd(II)-catalyzed enantioselective C-H activation has emerged as a versatile platform for constructing point, axial, and planar chirality. Herein, we present an unexpected discovery of a Pd-catalyzed enantioselective cascade ß,γ-methylene C(sp3)-H diarylation of free carboxylic acids using bidentate chiral mono-protected amino thioether ligands (MPAThio), enabling one-step synthesis of a complex chiral 9,10-dihydrophenanthrenes scaffolds with high enantioselectivity. In this process, two methylene C(sp3)-H bonds and three C(sp2)-H bonds were activated, leading to the formation of four C-C bonds and two chiral centers in one pot. A plausible catalytic pathway starts with enantioselective ß,γ-dehydrogenation to form chiral ß,γ-cyclohexene. Intriguingly, this olefin serves as a norbornene-type reagent (presumably assisted by the carboxyl directing effect), relaying two successive Catellani arylation reactions and a C-H alkylation reaction to furnish chiral 9,10-dihydrophenanthrenes along with meta-selective homocoupling products of iodoarene.

Plasma circulating tumour DNA is a better source for diagnosis and mutational analysis of IVLBCL than tissue DNA.

Diagnosis of intravascular large B-cell lymphoma (IVLBCL) is a challenge due to its heterogeneous clinical presentation and lack of specific markers. This retrospective study investigated the utility of circulating tumour DNA (ctDNA) sequencing for diagnosing IVLBCL and analysing its mutation landscape. A cohort of 34 IVLBCL patients enrolled and underwent plasma ctDNA targeted sequencing. The median plasma ctDNA concentration was 135.0 ng/mL, significantly higher than that in diffuse large B-cell lymphoma (DLBCL) controls. Correlations were found between ctDNA concentration and disease severity indicators, LDH and SF. Mutation analysis revealed frequent mutations in B-cell receptor and NF-κB signalling pathways, including MYD88 (56%), CD79B (44%), TNFAIP3 (38%) and IRF4 (29%). CNS involvement was significantly related with BCL6 and CD58 mutation. Patients with complicated hemophagocytic lymphohistiocytosis had significantly higher mutation rates in B2M. Comparison with DLBCL subtypes showed distinctive mutation profiles in IVLBCL. Moreover, plasma ctDNA detected more mutations with higher variant allele fraction than tissue DNA, suggesting its superiority in sensitivity and accessibility. Dynamic monitoring of ctDNA during treatment correlated with therapeutic responses. This study revealed the role of ctDNA in IVLBCL diagnosis, mutation analysis, and treatment monitoring, offering a promising avenue for improving patient diagnosis in this rare lymphoma subtype.

Versatile Copper-Catalyzed γ-C(sp3)-H Lactonization of Aliphatic Acids.

Site-selective C(sp3)-H oxidation is of great importance in organic synthesis and drug discovery. γ-C(sp3)-H lactonization of free carboxylic acids provides the most straightforward means to prepare biologically important lactone scaffolds from abundant and inexpensive carboxylic acids; however, a versatile catalyst for this transformation with a broad substrate scope remains elusive. Herein, we report a simple yet broadly applicable and scalable γ-lactonization reaction of free aliphatic acids enabled by a copper catalyst in combination with inexpensive Selectfluor as the oxidant. This lactonization reaction exhibits compatibility with tertiary, benzylic, allylic, methylene, and primary γ-C-H bonds, affording access to a wide range of structurally diverse lactones such as spiro, fused, and bridged lactones. Notably, exclusive γ-methylene C-H lactonization of cycloalkane carboxylic acids and cycloalkane acetic acids was observed, giving either fused or bridged γ-lactones that are difficult to access by other methods. δ-C-H lactonization was only favored in the presence of tertiary δ-C-H bonds. The synthetic utility of this methodology was demonstrated by the late-stage functionalization of amino acids, drug molecules, and natural products, as well as a two-step total synthesis of (iso)mintlactones (the shortest synthesis reported to date).

The skin circadian clock gene F3 as a potential marker for psoriasis severity and its bidirectional relationship with IL-17 signaling in keratinocytes.

OBJECTIVE: Psoriasis is an immune-mediated skin disease where the IL-17 signaling pathway plays a crucial role in its development. Chronic circadian rhythm disorder in psoriasis pathogenesis is gaining more attention. The relationship between IL and 17 signaling pathway and skin clock genes remains poorly understood. METHODS: GSE121212 with psoriatic lesion and healthy controls was used as the exploration cohort for searching analysis. Datasets GSE54456, GSE13355, GSE14905, GSE117239, GSE51440, and GSE137218 were applied to validation analysis. Single-cell RNA sequencing (scRNA-seq) dataset GSE173706 was used to explore the F3 expression and related pathway activities in single-cell levels. Through intersecting with high-expression DEGs, F3 was selected as the signature skin circadian gene in psoriasis for further investigation. Functional analyses, including correlation analyses, prediction of transcription factors, protein-protein interaction, and single gene GSEA to explore the potential roles of F3. ssGSEA algorithm was performed to uncover the immune-related characteristics of psoriasis. We further explored F3 expression in the specific cell population in scRNA-seq dataset, besides this, AUCell analysis was performed to explore the pathway activities and the results were further compared between the specific cell cluster. Immunohistochemistry experiment, RT-qPCR was used to validate the location and expression of F3, small interfering RNA (siRNA) transfection experiment in HaCaT, and transcriptome sequencing analysis were applied to explore the potential function of F3. RESULTS: F3 was significantly down-regulated in psoriasis and interacted with IL-17 signaling pathway. Low expression of F3 could upregulate the receptor of JAK-STAT signaling, thereby promoting keratinocyte inflammation. CONCLUSION: Our research revealed a bidirectional link between the skin circadian gene F3 and the IL-17 signaling pathway in psoriasis, suggesting that F3 may interact with the IL-17 pathway by activating JAK-STAT within keratinocytes and inducing abnormal intracellular inflammation.

High-Performance Solar-Blind Photodetector Based on (010)-Plane ß-Ga2O3 Thermally Oxidized from Nonpolar (110)-Plane GaN.

A high-performance planar structure metal-semiconductor-metal-type solar-blind photodetector (SBPD) was fabricated on the basis of (010)-plane ß-Ga2O3 thermally oxidized from nonpolar (110)-plane GaN. A full width at half maximum of 0.486° was achieved for the X-ray rocking curve associated with (020)-plane ß-Ga2O3, which is better than most reported results for the heteroepitaxially grown (-201)-plane ß-Ga2O3. As a result of the relatively high crystalline quality, a dark current as low as 6.30 × 10-12 A was achieved at 5 V, while the photocurrent reached 1.86 × 10-5 A under 254 nm illumination at 600 µW/cm2. As a result, the photo-to-dark current ratio, specific detectivity, responsivity, and external quantum efficiency were calculated to be 2.95 × 106, 2.39 × 1012 Jones, 3.72 A/W, and 1815%, respectively. Moreover, the SBPD showed excellent repeatability and stability in the time-dependent photoresponse characteristics with fast relaxation time constants for the rise and decay processes of only 0.238 and 0.062 s, respectively. This study provides a promising approach to fabricate the device-level (010)-plane ß-Ga2O3 film and a new way for the epitaxial growth of (010)-plane ß-Ga2O3 and (110)-plane GaN as mutual substrates.

Monolithic Integration of GaN-Based Transistors and Micro-LED.

Micro-LED is considered an emerging display technology with significant potential for high resolution, brightness, and energy efficiency in display applications. However, its decreasing pixel size and complex manufacturing process create challenges for its integration with driving units. Recently, researchers have proposed various methods to achieve highly integrated micro-structures with driving unit. Researchers take advantage of the high performance of the transistors to achieve low power consumption, high current gain, and fast response frequency. This paper gives a review of recent studies on the new integration methods of micro-LEDs with different types of transistors, including the integration with BJT, HEMT, TFT, and MOSFET.

Access to N-Aryl (Iso)quinolones via Aryne-Induced Three-Component Coupling Reaction.

N-Aryl (iso)quinolones are of increasing interest in material and medicinal chemistry, although general routes for their provision remain underexplored, especially when compared with its N-alkyl counterparts. Herein, we report a modular and transition-metal-free, aryne-induced three-component coupling protocol that allows the facile synthesis of structurally diverse N-aryl (iso)quinolones from readily accessible halo-(iso)quinolines in the presence of water. Preliminary results highlight the applicability of our method through scale-up synthesis, downstream derivatization, and flexible synthesis involving other types of aryne precursors.

PTPN2 inhibits the proliferation of psoriatic keratinocytes by dephosphorylation of STAT3.

Psoriasis is a recurrent and protracted disease that severely impacts the patient's physical and mental health. Thus, there is an urgent need to explore its pathogenesis to identify therapeutic targets. The expression level of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) was analyzed by immunohistochemistry techniques in psoriatic tissues and imiquimod-induced psoriatic mouse models. PTPN2 and signal transducer and activator of transcription 3 (STAT3) were overexpressed or silenced in human keratinocytes or an interleukin (IL)-6-induced psoriasis HaCaT cell model using overexpression plasmid transfection or small interfering RNA technology in vitro, and the effects of PTPN2 on STAT3, HaCaT cell function, and autophagy levels were investigated using reverse transcription-quantitative polymerase chain reaction, Western blot, Cell Counting Kit 8, 5-ethynyl-20-deoxyuridine, flow cytometry, and transmission electron microscopy. PTPN2 expression was found to be significantly downregulated in psoriatic tissues. Then, the in vitro antipsoriatic properties of PTPN2 were investigated in an IL-6-induced psoriasis-like cell model, and the results demonstrated that inhibition of keratinocyte proliferation by PTPN2 may be associated with elevated STAT3 dephosphorylation and autophagy levels. These findings provide novel insights into the mechanisms of autophagy in psoriatic keratinocytes and may be essential for developing new therapeutic strategies to improve inflammatory homeostasis in psoriatic patients.

Identification of potential biomarkers and infiltrating immune cells from scalp psoriasis.

BACKGROUND: Scalp psoriasis seriously affects the appearance and psychological status of patients. The aim of this study was to investigate the effect and potential mechanism of RPL9 and TIFA in scalp psoriasis, so as to provide a precise and effective way for the clinical treatment of scalp psoriasis. METHODS: The Gene Expression Omnibus (GEO) database was employed to download the GSE75343 dataset to search for differentially expressed genes (DEGs) in scalp psoriasis through Sangerbox. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) enrichment analysis, functional enrichment analysis, immune cell infiltration analysis, immune responses and correlation analysis with 12 hub genes were performed. Then, STRING was used to develop a protein-protein interaction (PPI) network, used Cytoscape to locate hub genes, and SVM-RFE and random forest were utilized to identified RPL9 as the targeted gene. TIFA-RPL9 interaction predictions were made viathe Open Targets Platform and Uniprot. Further, the RPL9 and TIFA expression, molecular mechanism, and function were assessed in scalp psoriasis. RESULTS: Immunohistochemistry, qPCR, and western blotting verified that RPL9 and TIFA were highly expressed in lesional tissues of scalp psoriasis and IL17A-stimulated HaCaT cells. RPL9 knockdown effectively suppressed the proliferative capacity of IL17A-stimulated HaCaT cells in the CCK8 assay. The co-immunoprecipitation results revealed that RPL9 could interact with TIFA in IL17A-stimulated HaCaT cells. In qPCR and western blotting, RPL9 knockdown significantly inhibited TIFA at the mRNA and protein levels in IL17A-stimulated HaCaT cells. In ELISA, the secretion of TNF-α was markedly inhibited after downregulating RPL9 in IL17A-stimulated HaCaT cells. CONCLUSION: To our knowledge, we have elucidated the expression and role of RPL9 and TIFA in scalp psoriatic skin and keratinocytes, and our findings confirm that RPL9 might act as a candidate therapeutic target for scalp psoriasis.

Cerebrospinal Fluid Interleukin-10 Biomarker for Vitreoretinal Lymphoma.

PURPOSE: To analyze the correlation between cerebrospinal fluid (CSF) interleukin-10 (IL-10) levels and the clinical characteristics in patients with vitreoretinal lymphoma (VRL). DESIGN: Retrospective observational case series. METHODS: Forty-one patients were diagnosed as VRL and underwent lumbar puncture for CSF examination. Aqueous humor cytokine detection, vitreous cytopathologic analysis, monoclonal gene rearrangement, and flow cytometry were performed. The CSF was assessed through biochemical and cytologic examination, flow cytometry, and cytokine detection. RESULTS: The median levels of aqueous humor IL-10 and IL-6 were 415.0 and 40.7 pg/mL. The median CSF levels of IL-10 and IL-6 were 35.7 and 3.5 pg/mL, respectively. IL-10 levels in CSF were higher than normal in 37 patients (90.2%) and higher in patients with intracranial lesions. The level of CSF IL-10 decreased after systemic treatment, and it rose before intracranial lesion onset or recurrence. The level of IL-10 in CSF was related to the duration of ocular symptoms, but was not related to the level of IL-10 in aqueous humor. There was no significant difference in CSF IL-10 levels between patients with and without anterior chamber inflammation or retinal lesions. In eyes with recurrent vitreoretinal lymphoma, the level of IL-10 in aqueous humor increased significantly, but there was no corresponding increase in the level of IL-10 in CSF. CONCLUSION: CSF IL-10 is a potentially important biomarker in VRL, especially in the monitoring of intracranial lesions.