Improved Gaussian basis sets for norm-conserving 4f-in-core pseudopotentials of trivalent lanthanides (Ln = Ce-Lu).

The first-principles quantum chemical computations often scale as Nk (N = basis sets; k = 1-4 for linear scaling, Hartree-Fock or density functional theory methods), which makes the development of accurate pseudopotentials and efficient basis sets necessary ingredients in modeling of heavy elements such as lanthanides and actinides. Recently, we have developed 4f-in-core norm-conserving pseudopotentials and associated basis sets for the trivalent lanthanides [Lu et al., J. Chem. Theory Comput. 19, 82-96 (2023)]. In the present paper, we present a unified approach to optimize high-quality Gaussian basis sets for modeling and simulations of condensed-phase systems. The newly generated basis sets not only capture the low total energy and fairly reasonable condition number of overlap matrix of lanthanide-containing systems, but also exhibit good transferability and reproducibility. These advantages ensure the accuracy of the basis sets while avoiding linear dependency concern of atom-centered basis sets. The performance of the basis sets is further illustrated in lanthanide molecular and condensed-phase systems by using Gaussian-plane wave density functional approach of CP2K. These new basis sets can be of particular interest to model structurally complicated lanthanide molecules, clusters, solutions, and solid systems.

The broad-spectrum deubiquitinating enzyme inhibitor PR-619 protects retinal ganglion cell and augments parkin-mediated mitophagy in experimental glaucoma.

Glaucoma is a leading cause of irreversible visual impairment worldwide, characterized by the progressive death of retinal ganglion cells (RGCs). Deubiquitinating enzyme (DUB) inhibitors have shown promise as pharmacological interventions for neurodegenerative disorders. Our study focuses on the pan-DUB inhibitor PR-619 and its potential neuroprotective effects on RGCs through modulation of parkin-mediated mitophagy in experimental glaucoma models. The results show that impaired mitophagy exists in RGCs of our experimental glaucomatous model. In vivo, PR-619 increased RGCs survival in glaucomatous rats. In vitro, it protected RGCs against excitotoxicity and reduced ubiquitin-specific protease (USP) 15 expression. Additionally, PR-619 upregulated parkin expression, increased LC3-II/LC3-I ratios, and elevated LAMP1 levels, indicating enhanced mitophagy in vivo and in vitro. Moreover, numbers of mitophagosomes were increased in optic nerves of PR-619-treated ocular hypertensive rats in vivo. Furthermore, parkin knockdown negated the salutary effects of PR-619 and attenuated expression of parkin-dependent mitophagy effectors in RGCs subjected to glutamate excitotoxicity in vitro. Collectively, these findings implicate augmented parkin-mediated mitophagy as the mechanistic substrate underscoring the neuroprotective capacity of PR-619 in experimental glaucoma. These revelations engender the prospect that pharmacological agents or biotherapeutics augmenting parkin-mediated mitophagy may proffer viable therapeutic modalities for glaucomatous neurodegeneration characterized by impaired mitophagy.

Theoretical Design of Thorium Nitride MXenes.

Actinides with 5f6d7s valence orbitals feature special physicochemical properties different from those of the other elements. Actinide-based two-dimensional (2D) materials combine the distinctive physics of actinides with the quantum size effect of 2D materials, but relevant studies are scarce. Since Th has a valence electron configuration of 6d27s2 like Ti, and Ti-based MXenes show excellent stability and versatile applications, whether Th can form stable MXenes has become an intriguing question. Herein, we designed Th2N, Th3N2, and Th4N3 MXenes and investigated their physical properties, functionalization, and potential applications using density functional theory. Their stabilities are validated by global minimum search, phonon spectra, ab initio molecular dynamics, enthalpy of formation, and energy above the hull. All the Th-N MXenes exhibit metallic properties and are stabilized by the electrostatic interaction between Th and N ions, as well as the covalent bonding interaction between the Th 6d/5f and N 2p/2s orbitals. The H-, O-, and F-functionalization3N2 MXene improve its stability while preserving its metallicity, and the O-functionalized Th3N2 MXene shows promising catalytic activity for hydrogen evolution. The thorium nitride MXenes enrich the family of actinide-based 2D materials and extend our understanding of the structures and properties induced by actinide elements in low-dimensional materials.

Risk prediction of diabetic retinopathy based on visit-to-visit fasting blood glucose indices.

Objective: The long-term glucose monitoring is essential to the risk assessment of diabetic retinopathy (DR), the aim of this study was to investigate the predictive ability of visit-to-visit fasting blood glucose (FBG) indices on the risk of DR. Methods: This was a community-based, cohort study conducted from 2013 to 2021. DR was diagnosed by digital fundus photography. The FPG indices included FBG, var. Associations of each FBG indices and DR were estimated using multinomial logistic regression models adjusting for confounders, and discrimination was determined by area under the curve (AUC). Predictive utility of different models was compared by changes in AUC, integrated discrimination improvement (IDI), and net reclassification index (NRI). Results: This study analyzed 5054 participants, the mean age was 46.26 ± 11.44 years, and 2620 (51.84%) were women. After adjustment for confounders, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for FBG, SD, CV, VIM, ARV, M-FBG, and cumulative FBG load were 1.62 (1.52-1.73), 2.74 (2.38-3.16), 1.78 (1.62-1.95), 1.11 (0.95-1.29), 1.72 (1.56-1.91), 2.15 (1.96-2.36), and 2.57 (2.31-2.85), respectively. The AUC of the model with separate cumulative FBG load and classical risk factors was 0.9135 (95%CI 0.8890-0.9380), and no substantive improvement in discrimination was achieved with the addition of other FBG indices once cumulative FBG load was in the model. Conclusions: Cumulative FBG load is adequate for capturing the glucose-related DR risk, and the predictive utility of cumulative FBG load is not significantly improved by adding or replacing other FBG indices in the assessment of DR risk.

Is pentavalent Pr(V) feasible in solid CsPrF6?

The oxidation state (OS) holds significant importance in the field of chemistry and serves as a crucial parameter for tracking electrons. Lanthanide (Ln) elements predominately exhibit a +III oxidation state, with a few elements such as Ce, Pr, Nd, Tb, and Dy able to achieve a +IV oxidation state. Over the past century, numerous attempts to synthesize Pr(V) have been made without success until recent reports on Pr(V) oxides and nitride-oxide in the gas phase expanded our understanding of Ln elements. However, the formation of Pr(V) in the condensed phase remains an open question. In this work, based on advanced quantum chemical investigations, we predict that formation of the solid-state CsPrVF6 from Pr(III) and Pr(IV) complexes is exothermic, indicating that CsPrVF6 is stable. The crystal structure comprises [PrF6]- octahedral clusters occupying the interstitial spaces of Cs cations. Electronic structure analysis reveals that the CsPrF6 crystal has a closed-shell structure and that Pr reaches its highest oxidation state of +V. The results indicate that the existence of Pr(V) in solid-state Ln fluorides is not impossible, which enriches our understanding of high-valence Ln compounds.

Quantitative Study on the Anticollapse Ability of Casing in Shale Gas Wells under Complex Load Conditions.

Implementing novel technologies, including the "well factory" model and zipper fracturing techniques, has become prevalent in shale gas development. During completion operations such as lowering casing and multistage fracturing, the casing is subjected to many complex loads, reducing its strength and increasing the risk of casing deformation. By establishing a casing wear model and conducting multistage cyclic loading experiments and numerical simulations, we analyzed the change rule of casing anticollapse strength under complex loads, developed a calculation method for casing comprehensive anticollapse ability under complex loads, and applied the method to an illustrative calculation. The study shows that the wear effect during completion has a negligible impact on the strength of the casing. The casing anticollapse strength exhibits a linear decline in correlation with the number of cycles. The zipper fracturing operation resulted in a nonuniform distribution of geo-stress around the well, and the casing anticollapse strength demonstrated a nearly linear decline in correlation with the nonuniformity of geo-stress. In the presence of both internal and external effects, the casing anticollapse strength exhibited a decline exceeding 15%, thereby increasing the risk of casing deformation. This research method can provide computational guidance for preventing casing deformation in field fracturing construction.

Efficacy and Safety of Pioglitazone/Metformin Fixed-Dose Combination Versus Uptitrated Metformin in Patients with Type 2 Diabetes without Adequate Glycemic Control: A Randomized Clinical Trial.

INTRODUCTION: We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. METHODS: A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500 mg) or the control group (uptitrated metformin, 2000-2500 mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. RESULTS: In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. CONCLUSIONS: Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. TRIAL REGISTRATION NUMBER: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).

Regulating the Double-Way Traffic of Cations and Anions in Ambipolar Polymer Cathodes for High-Performing Aluminum Dual-Ion Batteries.

The strong Coulombic interactions between Al3+ and traditional inorganic crystalline cathodes present a significant obstacle in developing high-performance rechargeable aluminum batteries (RABs) that hold promise for safe and sustainable stationary energy storage. While accommodating chloroaluminate ions (AlCl4 -, AlCl2+, etc.) in redox-active organic compounds offers a promising solution for RABs, the issues of dissolution and low ionic/electronic conductivities plague the development of organic cathodes. Herein, electron donors are synthetically connected with acceptors to create crosslinked, bipolar-conjugated polymer cathodes. These cathodes exhibit overlapped redox potential ranges for both donors and acceptors in highly concentrated AlCl3-based ionic liquid electrolytes. This approach strategically enables on-site doping of the polymer backbones during redox reactions involving both donor and acceptor units, thereby enhancing the electron/ion transfer kinetics within the resultant polymer cathodes. Based on the optimal donor/acceptor combination, the bipolar polymer cathodes can deliver a high specific capacity of 205 mAh g-1 by leveraging the co-storage of AlCl4 - and AlCl2+. The electrodes exhibit excellent rate performance, a stable cycle life of 60 000 cycles, and function efficiently at high mass loadings, i.e., 100 mg cm-2, and at low temperatures, i.e., -30 °C. The findings exemplify the exploration of high-performing conjugated polymer cathodes for RABs through rational structural design.

Network pharmacology and experimental verification revealing valnemulin alleviates DSS-induced ulcerative colitis by inhibiting intestinal senescence.

Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence globally. Senescence is characterized by a specific chronic, low-grade, "sterile" inflammatory state known as inflammaging, suggesting that senescence may exacerbate the severity of UC. However, the link between UC and senescence remains unclear. Valnemulin (VAL) is a semi-synthetic derivative of a naturally occurring diterpenoid antibiotic (pleuromutilin), which can inhibit peptidyl transferase. Studies investigating the potential of valnemulin to inhibit senescence and alleviate colitis are currently limited. In this study, we revealed that dextran sulfate sodium (DSS), an inducer of UC, induces senescence in both colon epithelial NCM460 cells and colon tissues. Additionally, VAL, identified from a compound library, exhibited robust anti-senescence activity in DSS-treated NCM460 cells. Identified in our study as an anti-senescence agent, VAL effectively mitigated DSS-induced UC and colonic senescence in mice. Through network pharmacology analysis and experimental validation, the potential signaling pathway (AMPK/NF-κB) for VAL in treating UC was identified. We discovered that DSS significantly inhibited the AMPK signaling pathway and activated the NF-κB signaling pathway. However, supplementation with VAL remarkably restored AMPK activity and inhibited the NF-κB signaling pathway, which led to the inhibition of senescence. In summary, our study demonstrated that DSS-induced UC stimulates the senescence of colonic tissues, and VAL can effectively alleviate DSS-induced colonic damage and reduce colonic senescence. Our research findings provide a new perspective for targeting anti-senescence in the treatment of UC.

Long Non-Coding RNA PVT1 Facilitates Radiation-Induced Vascular Endothelial Cell Injury through Sponging MicroRNA-9-5p.

Radiotherapy is a common therapeutic strategy for various solid tumors, with vascular endothelial injury being a common side effect. The study aimed to examine the effect of long non-coding RNA PVT1 on radiation-induced vascular endothelial cell injury, and explore the possible underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were exposed to different doses of X ray to mimic radiation. LncRNA and miRNA levels were detected via qRT-PCR. Interaction between lncRNA and miRNAs was determined through dual-luciferase reporter assay. Statistical processing was conducted using student's t test between two groups and one-way ANOVA among multiple groups, and P < 0.05 means a significant difference. GO and KEGG were performed for the function and pathway enrichment analysis. LncRNA PVT1 elevated along with the increase of radiation dose in HUVECs. Poorly expressed lncRNA PVT1 promotes cell viability and inhibits oxidative stress. PVT1 serves as a competitive endogenous RNA (ceRNA) of miR-9-5p. miR-9-5p inhibitor inverted the influence of PVT1 knockdown on radiation-stimulated cell apoptosis and oxidative stress in HUVECs. KEGG analysis identified significant enrichment of the MAPK signaling pathway among overlapping target genes of miR-9-5p. LncRNA PVT1 knockdown alleviated radiation-induced vascular endothelial injury via sponging miR-9-5p. The underlying mechanism might be probably MAPK signaling-related.

Iodinated gadolinium-gold nanomaterial as a multimodal contrast agent for cartilage tissue imaging.

Cartilage damage, a common cause of osteoarthritis, requires medical imaging for accurate diagnosis of pathological changes. However, current instruments can acquire limited imaging information due to sensitivity and resolution issues. Therefore, multimodal imaging is considered an alternative strategy to provide valuable images and analyzes from different perspectives. Among all biomaterials, gold nanomaterials not only exhibit outstanding benefits as drug carriers, in vitro diagnostics, and radiosensitizers, but are also widely used as contrast agents, particularly for tumors. However, their potential for imaging cartilage damage is rarely discussed. In this study, we developed a versatile iodinated gadolinium-gold nanomaterial, AuNC@BSA-Gd-I, and its radiolabeled derivative, AuNC@BSA-Gd-131I, for cartilage detection. With its small size, negative charge, and multimodal capacities, the probe can penetrate damaged cartilage and be detected or visualized by computed tomography, MRI, IVIS, and gamma counter. Additionally, the multimodal imaging potential of AuNC@BSA-Gd-I was compared to current multifunctional gold nanomaterials containing similar components, including anionic AuNC@BSA, AuNC@BSA-I, and AuNC@BSA-Gd as well as cationic AuNC@CBSA. Due to their high atomic numbers and fluorescent emission, AuNC@BSA nanomaterials could provide fundamental multifunctionality for imaging. By further modifying AuNC@BSA with additional imaging materials, their application could be extended to various types of medical imaging instruments. Nonetheless, our findings showed that each of the current nanomaterials exhibited excellent abilities for imaging cartilage with their predominant imaging modalities, but their versatility was not comparable to that of AuNC@BSA-Gd-I. Thus, AuNC@BSA-Gd-I could be served as a valuable tool in multimodal imaging strategies for cartilage assessment.

The key point of transsphenoidal surgery for infradiaphragmatic craniopharyngioma：Better sellar diaphragm resection.

Background: Craniopharyngiomas have a high recurrence rate and a poor prognosis, and the key methods for reducing recurrences are unknown. The aim of this study was to explore the key points of microscopic or endoscopic transsphenoidal surgery used to treat infradiaphragmatic craniopharyngiomas. Methods: We reviewed the medical records of patients with infradiaphragmatic craniopharyngiomas who were admitted to Peking Union Medical College Hospital between 2011 and 2018. Results: When considering tumor location, all 34 patients had intrasellar tumors, with 19 of them exhibiting suprasellar extensions. Of the 34 patients, 24 patients underwent resection under the microscope and the remaining 10 patients underwent transsphenoidal endoscopic surgery. Gross total tumor resection was achieved in 16 patients. Twelve patients underwent invaded sellar diaphragm resection, while the remaining 22 patients were not. Cerebrospinal fluid leaks occurred during surgery in 18 patients. Visual acuity improved in two patients. After an average follow-up of 31.1 months, 13 patients experienced tumor recurrence. The short term recurrence rate in the sellar diaphragm resection group was significantly lower compared to the non-resected group (P < 0.001). Moreover, based on distinct surgical methods, the endoscope group displayed a reduced short term recurrence rate compared to the microscope group (P = 0.0048). Conclusion: Invaded sellar diaphragm resection emerges as a pivotal maneuver in craniopharyngioma surgery, substantively influencing tumor recurrence. Capitalizing on the advantageous angled lens of endoscopes, surgeons can achieve heightened visualization. Significantly, the endoscopic approach exhibits a superior capacity to curtail recurrence, while effectively managing potential complications, when contrasted with the microscope group.

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in iNFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

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In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.

Probabilistic sunspot predictions with a gated recurrent units-based combined model guided by pinball loss.

Sunspots play a crucial role in both weather forecasting and the monitoring of solar storms. In this work, we propose a novel combined model for sunspot prediction using improved gated recurrent units (GRU) guided by pinball loss for probabilistic forecasts. Specifically, we optimize the GRU parameters using the slime mould algorithm and employ a seasonal-trend decomposition procedure based on loess to tackle challenges related to sequence prediction, such as self-correlations and non-stationarity. To address prediction uncertainty, we replace the traditional l 2 -norm loss with pinball loss. This modification extends the conventional GRU-based point forecasting to a probabilistic framework expressed as quantiles. We apply our proposed model to analyze a well-established historical sunspot dataset for both single- and multi-step ahead forecasting. The results demonstrate the effectiveness of our combined model in predicting sunspot values, surpassing the performance of other existing methods.

Efficacy and Safety of Ganyushu Granule in Treatment of Premenstrual Syndrome with Gan (Liver) Depression and Qi Stagnation Syndrome: A Randomized, Double-Blind, Multicenter, Phase-II Clinical Trial.

OBJECTIVE: To confirm the efficacy and safety of Ganyushu Granule (GYSG) in treating premenstrual syndrome (PMS) in patients with Gan (Liver) depression and qi stagnation syndrome (GDQSS) and determine its effective dosage. METHODS: From June 2018 to March 2021, a total of 240 PMS women with GDQSS were included and randomly divided into 3 groups in a 1:1:1 ratio using central block randomization: high-dose GYSG group (n=78, GYSG 2 packs/time), low-dose GYSG group (n=82, GYSG and its simulant 1 pack/time), and placebo group (n=80, GYSG simulant 2 packs/time). Treatment with GYSG or placebo was given thrice daily and for up to 3 menstrual cycles. Primary outcomes were PMS diary (PMSD) score and premenstrual tension syndrome self-rating scale (PMTS). Secondary outcomes were Chinese medicine (CM) syndrome efficacy. PMSD, PMTS, and efficacy of CM were evaluated with menstrual cycles during the treatment period. Outcome indicators were analyzed after each menstrual cycle. All analyses were performed using an intention-to-treat method, and clinical safety was assessed. RESULTS: Of the 216 patients included in the effectiveness analysis, 70, 75, and 71 patients were in the high-, low-dose GYSG, and placebo groups, respectively. From the 2nd treatment cycle, the change in PMSD scores in the high- and low-dose groups was lower than that in the placebo group (P<0.05). PMTS scores in the high-dose GYSG group after the 1st treatment cycle was lower than that in the placebo group (P<0.05), while after the 3rd treatment cycle, that in the low-dose group was lower than that in the placebo group (P<0.05). After the 2nd treatment cycle, the high-dose GYSG group had the best CM syndrome efficacy (P<0.05). No serious adverse reactions were reported. CONCLUSIONS: GYSG was safe and well-tolerated at both doses for treating PMS patients with GDQSS. High-dose GYSG might be the optimal dose for a phase III trial. (Registration No. ChiCTR1800016595).

Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

BACKGROUND: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. METHODS: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). RESULTS: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased ß-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). CONCLUSIONS: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

The impact of skeletal muscle index at the third lumbar spine on nosocomial deterioration and short-term prognosis in acute pancreatitis: a retrospective observational study.

Objective: To investigate the impact of the third lumbar skeletal muscle index (L3-SMI) assessed by CT on the in-hospital severity and short-term prognosis of acute pancreatitis. Methods: A total of 224 patients with severe acute pancreatitis admitted to Yantaishan Hospital from January 2021 to June 2022 were selected as the subjects. Based on the in-hospital treatment outcomes, they were divided into a mortality group of 59 cases as well as a survival group of 165 cases. Upon admission, general information such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, along with the abdominal CT images of each patient, were analyzed. The L3-SMI was calculated, and the Modified CT Severity Index (MCTSI) and Balthazar CT grade were used to assess the severity of in-hospital complications of acute pancreatitis. The evaluation value of L3-SMI for the prognosis of severe acute pancreatitis was analyzed, as well as the factors influencing the prognosis of severe acute pancreatitis. Results: No statistically significant differences in gender, age, BMI, etiology, duration of anti-inflammatory drug use, and proportion of surgical patients between the survival and mortality groups were observed. But the mortality group showed higher proportions of patients with an elevated APACHE II score upon admission, mechanical ventilation, and renal replacement therapy, compared to the survival group, with statistically significant differences (P < 0.001). Furthermore, the mortality group had higher MCTSI scores (6.42 ± 0.69) and Balthazar CT grades (3.78 ± 0.45) than the survival group, with statistically significant differences (P < 0.001). The mortality group also had a lower L3-SMI (39.68 ± 3.25) compared to the survival group (42.71 ± 4.28), with statistically significant differences (P < 0.001). L3-SMI exhibited a negative correlation with MCTSI scores and Balthazar CT grades (r = -0.889, -0.790, P < 0.001). Logistic regression analysis, with mortality of acute pancreatitis patients as the dependent variable and MCTSI scores, Balthazar CT grades, L3-SMI, APACHE II score upon admission, mechanical ventilation, and renal replacement therapy as independent variables, revealed that MCTSI scores and L3-SMI were risk factors for mortality in acute pancreatitis patients (P < 0.001). Logistic regression analysis using the same variables confirmed that all these factors were risk factors for mortality in acute pancreatitis patients. Conclusion: This study confirmed that diagnosing muscle depletion using L3-SMI is a valuable radiological parameter for predicting in-hospital severity and short-term prognosis in patients with acute pancreatitis.

Visible-Light-Promoted Deoxygenative Alkylation of Quinoxalin-2(1H)-ones with Activated Alcohols.

A one-pot strategy for deoxygenative alkylation of alcohols with quinoxalin-2(1H)-ones was developed by using xanthate salts as alcohol-activating groups for radical generation in the presence of tricyclohexylphosphine under visible-light-promoted conditions. The remarkable features of this reaction include a broad substrate scope, excellent functional group tolerance, mild conditions, and simple operation. Moreover, the synthetic utility of this reaction was validated by the success of two-step one-pot reactions, scale-up synthesis, and chemoselective radical monodeoxygenation of diols.