LncRNA-SERB promotes vasculogenic mimicry (VM) formation and tumor metastasis in renal cell carcinoma.

A growing body of evidence shows that vasculogenic mimicry (VM) is closely related to the invasion and metastasis of many tumor cells. Although the estrogen receptor (ER) can promote initiation and progression of renal cell carcinoma (RCC), how the downstream biomolecules are involved, and the detailed mechanisms of how ER expression is elevated in RCC remain to be further elucidated. Here, we discovered that long noncoding RNA (LncRNA)-SERB is highly expressed in tumor cells of RCC patients. We used multiple RCC cells and an in vivo mouse model for our study, and results indicated that LncRNA-SERB could boost RCC VM formation and cell invasion in vitro and in vivo. Although a previous report showed that ERß can affect the VM formation in RCC, it is unclear which factor could upregulate ERß. This is the first study to show LncRNA-SERB can be the upstream regulator of ERß to control RCC progression. Mechanistically, LncRNA-SERB may increase ERß via binding to the promoter area, and ERß functions through transcriptional regulation of zinc finger E-box binding homeobox 1 (ZEB1) to regulate VM formation. These results suggest that LncRNA-SERB promotes RCC cell VM formation and invasion by upregulating the ERß/ZEB1 axis and that therapeutic targeting of this newly identified pathway may better inhibit RCC progression.

Nerve growth factor promote osteogenic differentiation of dental pulp stem cells through MEK/ERK signalling pathways.

Nerve growth factor (NGF) and its receptor, tropomyosin receptor kinase A (TrkA), are known to play important roles in the immune and nervous system. However, the effects of NGF on the osteogenic differentiation of dental pulp stem cells (DPSCs) remain unclear. This study aimed to investigate the role of NGF on the osteogenic differentiation of DPSCs in vitro and the underlying mechanisms. DPSCs were cultured in osteogenic differentiation medium containing NGF (50 ng/mL) for 7 days. Then osteogenic-related genes and protein markers were analysed using qRT-PCR and Western blot, respectively. Furthermore, addition of NGF inhibitor and small interfering RNA (siRNA) transfection experiments were used to elucidate the molecular signalling pathway responsible for the process. NGF increased osteogenic differentiation of DPSCs significantly compared with DPSCs cultured in an osteogenic-inducing medium. The NGF inhibitor Ro 08-2750 (10 µM) and siRNA-mediated gene silencing of NGF receptor, TrkA and ERK signalling pathways inhibitor U0126 (10 µM) suppressed osteogenic-related genes and protein markers on DPSCs. Furthermore, our data revealed that NGF-upregulated osteogenic differentiation of DPSCs may be associated with the activation of MEK/ERK signalling pathways via TrkA. Collectively, NGF was capable of promoting osteogenic differentiation of DPSCs through MEK/ERK signalling pathways, which may enhance the DPSCs-mediated bone tissue regeneration.

An Ultrastable Low-Temperature Na Metal Battery Enabled by Synergy between Weakly Solvating Solvents.

The low ionic conductivity and high desolvation barrier are the main challenges for organic electrolytes in rechargeable metal batteries, especially at low temperatures. The general strategy is to couple strong-solvation and weak-solvation solvents to give balanced physicochemical properties. However, the two challenges described above cannot be overcome at the same time. Herein, we combine two different kinds of weakly solvating solvents with a very low desolvation energy. Interestingly, the synergy between the weak-solvation solvents can break the locally ordered structure at a low temperature to enable higher ionic conductivity compared to those with individual solvents. Thus, facile desolvation and high ionic conductivity are achieved simultaneously, significantly improving the reversibility of electrode reactions at low temperatures. The Na metal anode can be stably cycled at 2 mA cm-2 at -40 °C for 1000 h. The Na||Na3V2(PO4)3 cell shows the reversible capacity of 64 mAh g-1 at 0.3 C after 300 cycles at -40 °C, and the capacity retention is 86%. This strategy is applicable to other sets of weak-solvation solvents, providing guidance for the development of electrolytes for low-temperature rechargeable metal batteries.

Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors.

The increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC50 = 1.98 ± 0.66 µM). Subsequent exploration in structural activity relationships led to the discovery of compound B12 that demonstrated the increased enzymatic inhibitory activity (IC50 = 0.29 ± 0.02 µM). Furthermore, B12 exhibited robust inhibitory effects on the proliferation of MDA-MB-468, NCI-H1975, HT1080 and PC9 cells that overexpress PHGDH. Additionally, using a [U-13C6]-glucose tracing assay, B12 was found to reduce the production of glucose-derived serine in MDA-MB-468 cells. Finally, mass spectrometry-based peptide profiling, mutagenesis experiment and molecular docking study collectively suggested that B12 formed a covalent bond with Cys421 of PHGDH.

Evaluation of three prediction formulas of 24-hour urinary sodium excretion in Chinese residents: a systematic review and meta-analysis.

OBJECTIVE: To determine the appropriateness of three widely used formulas estimating 24-h urinary Na (24hUNa) from spot urine samples in the Chinese population. DESIGN: Systematic review and meta-analysis. SETTING: Literature review was conducted to identify studies for estimating 24hUNa using the Kawasaki, Tanaka and INTERSALT formulas simultaneously in PubMed, Embase and the Cochrane library databases. The mean difference (MD) and correlation coefficients (r) between measures and estimates from different formulas were assessed. PARTICIPANTS: Information extraction and quality assessment were performed in thirteen studies involving 8369 subjects. RESULTS: Two studies which affected the overall robustness were excluded in the 'leave-one-out' sensitivity analyses. Within the final meta-analysis included eleven studies and 7197 participants, 36·07 mmol/d (95 %CI 16·89, 55·25) of MD was observed in the Kawasaki formula, and -19·62 mmol/d (95 %CI -37·37, -1·87) in the Tanaka formula and -35·78 mmol/d (95 %CI -50·76, -20·80) in the INTERSALT formula; a pooled r-Fisher's Z of 0·39 (95 %CI 0·32, 0·45) in the Kawasaki formula, 0·43 (95 %CI 0·37, 0·49) in the Tanaka formula and 0·36 (95 %CI 0·31, 0·42) in the INTERSALT formula. Subgroup analyses were conducted to explore the possible factors affecting the accuracy of the formula estimation from three mainly aspects: population types, Na intake levels and urine specimen types. CONCLUSIONS: The meta-analysis suggested that the Tanaka formula performed a more accurate estimate in Chinese population. Time of collecting spot urine specimens and Na intake level of the sample population might be the main factors affecting the accuracy of the formula estimation.

Manipulation of path state based on spatiotemporal dielectric metasurface.

In this work, a spatiotemporal metasurface is proposed to manipulate the path of photons flexibly. The spatial modulation is induced by the rectangle silicon units aligned on silica in a manner with a phase gradient only for y-polarized photons, and the temporal modulation is contributed by the pumps of constructing Kerr dynamic gratings. By quantizing designed metasurfaces, the analytical solutions of output photon states can be derived correspondingly. Reversal design could be implemented by tailoring the profile of higher harmonics to infer the intensity of pumps, size of meta-atoms, and initial state. The path-polarization entanglement and correlations of output photons are realized, and then a CNOT gate is obtained by utilizing the deflection of the photon path. This work provides a scheme to deal with the spatiotemporal metasurfaces and expands the applications of metasurfaces in the quantum realm.

A Retrospective Cohort Study of vNOTES Extraperitoneal Versus Laparoscopic Sacral Hysteropexy With Uterine Preserving Regarding Surgical Outcomes and 2 Year Follow-up Results.

STUDY OBJECTIVE: To explore the effectiveness of transvaginal natural orifice transluminal endoscopic surgery extraperitoneal sacral hysteropexy (vNOTES-ESH) in women with symptomatic uterine prolapse over a 2 year follow-up. DESIGN: Retrospective cohort study. SETTING: Gynecological minimally invasive center. PATIENTS: Women undergoing sacral hysteropexy either by vNOTES (n = 25) or laparoscopic (n = 74) between November 2016 and December 2020. INTERVENTIONS: Both vNOTES-ESH and laparoscopic sacral hysteropexy (LAP-SH) were used for uterine prolapse. Demographic data, operative characteristics, perioperative outcomes, and follow-up information 2 years postsurgery in the 2 groups were retrospectively evaluated. RESULTS: Both procedures showed similar operation time, estimated blood loss, hospital stays, and pain scores (p >0.05). During a median follow-up of 59 (24-72) months, the surgical success rate was 96% for vNOTES-ESH and 97.3% for LAP-SH (p >0.05), with no differences in anatomical position or pelvic organ function after the operation. Women in the LAP-SH group experienced more bothersome symptoms of constipation compared to those in the vNOTES-ESH group (5.41% vs 0, p <0.05). Lastly, 1 case in the vNOTES-ESH group had a mesh exposed area of less than 1 cm2, and 1 patient in the LAP-SH group experienced stress incontinence. CONCLUSIONS: In this retrospective study, vNOTES-ESH met our patients' preference for uterine preservation and was a successful and effective treatment for uterine prolapse, providing good functional improvement in our follow-up. This procedure should be considered as an option for patients with pelvic organ prolapse.

Genome-Wide Identification of Vitellogenin Gene Family and Comparative Analysis of Their Involvement in Ovarian Maturation in Exopalaemon carinicauda.

Vitellogenin (Vtg) is a precursor of yolk proteins in egg-laying vertebrates and invertebrates and plays an important role in vitellogenesis and embryonic development. However, the Vtg family remains poorly characterized in Exopalaemon carinicauda, a major commercial mariculture species found along the coasts of the Yellow and Bohai Seas. In this study, 10 Vtg genes from the genomes of E. carinicauda were identified and characterized. Phylogenetic analyses showed that the Vtg genes in crustaceans could be classified into four groups: Astacidea, Brachyra, Penaeidae, and Palaemonidae. EcVtg genes were unevenly distributed on the chromosomes of E. carinicauda, and a molecular evolutionary analysis showed that the EcVtg genes were primarily constrained by purifying selection during evolution. All putative EcVtg proteins were characterized by the presence of three conserved functional domains: a lipoprotein N-terminal domain (LPD_N), a domain of unknown function (DUF1943), and a von Willebrand factor type D domain (vWD). All EcVtg genes exhibited higher expression in the female hepatopancreas than in other tissues, and EcVtg gene expression during ovarian development suggested that the hepatopancreas is the main synthesis site in E. carinicauda. EcVtg1a, EcVtg2, and EcVtg3 play major roles in exogenous vitellogenesis, and EcVtg3 also plays a major role in endogenous vitellogenesis. Bilateral ablation of the eyestalk significantly upregulates EcVtg mRNA expression in the female hepatopancreas, indicating that the X-organ/sinus gland complex plays an important role in ovarian development, mostly by inducing Vtg synthesis. These results could improve our understanding of the function of multiple Vtg genes in crustaceans and aid future studies on the function of EcVtg genes during ovarian development in E. carinicauda.

Optimization of an Ultrasound-Assisted Extraction Technique and the Effectiveness of the Sunscreen Components Isolated from Bletilla striata.

Bletilla striata is the dried tuber of B. striata (Thund.) Reichb.f., which has antibacterial, anti-inflammatory, anti-tumor, antioxidant and wound healing effects. Traditionally, it has been used for hemostasis therapy, as well as to treat sores, swelling and chapped skin. In this study, we used the ultraviolet (UV) absorbance rate of B. striata extracts as the index, and the extraction was varied with respect to the solid-liquid ratio, ethanol concentration, ultrasonic time and temperature in order to optimize the extraction process for its sunscreen components. The main compounds in the sunscreen ingredients of Baiji (B. striata) were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry. The sunscreen properties were subsequently evaluated in vitro using the 3M tape method. The results show that the optimal extraction conditions for the sunscreen components of B. striata were a solid-liquid ratio of 1:40 (g/mL), an ethanol concentration of 50%, an ultrasonic time of 50 min and a temperature of 60 °C. A power of 100 W and an ultrasonic frequency of 40 Hz were used throughout the experiments. Under these optimized conditions, the UV absorption rate of the isolated sunscreen components in the UVB region reached 84.38%, and the RSD was 0.11%. Eighteen compounds were identified, including eleven 2-isobutyl malic acid glucose oxybenzyl esters, four phenanthrenes, two bibenzyl and one α-isobutylmalic acid. An evaluation of the sunscreen properties showed that the average UVB absorption values for the sunscreen samples from different batches of B. striata ranged from 0.727 to 1.201. The sunscreen ingredients of the extracts from B. striata had a good UV absorption capacity in the UVB area, and they were effective in their sunscreen effects under medium-intensity sunlight. Therefore, this study will be an experimental reference for the extraction of sunscreen ingredients from the B. striata plant, and it provides evidence for the future development of B. striata as a candidate cosmetic raw material with UVB protection properties.

[Clinical study on growth impairment induced by oral glucocorticoids based on FGF23/Klotho homeostasis observations]. / 基于FGF23/Klothoç¨³æ€è§‚å¯Ÿå£æœç³–çš®è´¨æ¿€ç´ è‡´ç”Ÿé•¿éšœç¢çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To observe the correlation between growth impairment induced by long-term oral glucocorticoids (GC) therapy and the ratio of FGF23/Klotho in children with primary nephrotic syndrome (PNS). METHODS: A prospective study was conducted on 56 children with GC-sensitive PNS who had discontinued GC therapy for more than 3 months and revisited the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine between June 2022 and December 2022. After monitoring qualitative and quantitative urine protein levels upon admission, the children with proteinuria relapse were treated with GC (GC group; n=29), while those without relapse did not receive GC treatment (non-GC group; n=27). In addition, 29 healthy children aged 3 to prepuberty were selected as the control group. Height, bone age, growth rate, and the FGF23/Klotho ratio were compared among the groups. The correlations of the FGF23/Klotho ratio with height, bone age, and growth rate were analyzed. RESULTS: The FGF23/Klotho ratio in the GC group was significantly higher than that in the non-GC group after 1 month of GC therapy (P<0.05), and the height and bone age growth rates within 6 months were lower than those in the non-GC group (P<0.05). Correlation analysis showed significant negative correlations between the FGF23/Klotho ratio after 1 month of treatment and the growth rates of height and bone age within 6 months in children with PNS (r=-0.356 and -0.436, respectively; P<0.05). CONCLUSIONS: The disturbance in FGF23/Klotho homeostasis is one of the mechanisms underlying the growth impairment caused by long-term oral GC therapy.

FDC-SP as a diagnostic and prognostic biomarker and modulates immune infiltrates in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC), one of the top 10 causes of cancer death, is responsible for more than 90% of all cases of primary renal cancer worldwide. Follicular dendritic cell-secreted protein (FDC-SP) specifically binds to activated B cells and regulates the generation of antibodies. It is also thought to promote cancer cell invasion and migration, which could help with tumor metastases. This study aimed to assess the efficacy of FDC-SP in the diagnosis and prognosis of RCC and to investigate the relationship between immune infiltration in RCC and these outcomes. RESULTS: RCC tissues had significantly higher levels of FDC-SP protein and mRNA than normal tissues. The high level of FDC-SP expression was linked to the T stage, histological grade, pathological stage, N stage, M stage, and OS event. Functional enrichment analysis identified the major pathways that were enriched as immune response regulation, complement, and coagulation. Immunological checkpoints and immune cell infiltration were observed to substantially correlate with the levels of FDC-SP expression. FDC-SP expression levels showed the ability to precisely distinguish high-grade or high-stage renal cancer (area under the curve (AUC) = 0.830, 0.722), and RCC patients with higher FDC-SP expression levels had worse prognoses. The AUC values for one-, two-, and five-year survival rates were all greater than 0.600. Moreover, the FDC-SP expression is an independent predictive biomarker of OS in RCC patients. CONCLUSION: FDC-SP may be a prospective therapeutic target in RCC as well as a possible diagnostic and prognostic biomarker associated with immune infiltration.

Ligand-Assistant Iced Photocatalytic Reduction to Synthesize Atomically Dispersed Cu Implanted Metal-Organic Frameworks for Photo-Enhanced Uranium Extraction from Seawater.

Uranium extraction from natural seawater is one of the most promising routes to address the shortage of uranium resources. By combination of ligand complexation and photocatalytic reduction, porous framework-based photocatalysts have been widely applied to uranium enrichment. However, their practical applicability is limited by poor photocatalytic activity and low adsorption capacity. Herein, atomically dispersed Cu implanted UiO-66-NH2 (Cu SA@UiO-66-NH2 ) photocatalysts are prepared via ligand-assistant iced photocatalytic reduction route. N-Cu-N moiety acts as an effective electron acceptor to potentially facilitate charge transfer kinetics. By contrast, there exist Cu sub-nanometer clusters by the typical liquid phase photoreduction, resulting in a relatively low photocatalytic activity. Cu SA@UiO-66-NH2 adsorbents exhibit superior antibacterial ability and improved photoreduction conversion of the adsorbed U(VI) to insoluble U(IV), leading to a high uranium sorption capacity of 9.16 mg-U/g-Ads from natural seawater. This study provides new insight for enhancing uranium uptake by designing SA-mediated MOF photocatalysts.

Transition Metal-Free Aromatic C-H, C-N, C-S and C-O Borylation.

Aromatic organoboron compounds are highly valuable building blocks in organic chemistry. They were mainly synthesized through aromatic C-H and C-Het borylation, in which transition metal-catalysis dominate. In the past decade, with increasing attention to sustainable chemistry, numerous transition metal-free C-H and C-Het borylation transformations have been developed and emerged as efficient methods towards the synthesis of aromatic organoboron compounds. This account mainly focuses on recent advances in transition metal-free aromatic C-H, C-N, C-S, and C-O borylation transformations and provides insights to where further developments are required.

Tetrandrine synergizes with MAPK inhibitors in treating KRAS-mutant pancreatic ductal adenocarcinoma via collaboratively modulating the TRAIL-death receptor axis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies lacking effective therapies. KRAS mutations that occur in over 90% of PDAC are major oncogenic drivers of PDAC. The MAPK signaling pathway plays a central role in KRAS-driven oncogenic signaling. However, pharmacological inhibitors of the MAPK pathway are poorly responded in KRAS-mutant PDAC, raising a compelling need to understand the mechanism behind and to seek new therapeutic solutions. Herein, we perform a screen utilizing a library composed of 800 naturally-derived bioactive compounds to identify natural products that are able to sensitize KRAS-mutant PDAC cells to the MAPK inhibition. We discover that tetrandrine, a natural bisbenzylisoquinoline alkaloid, shows a synergistic effect with MAPK inhibitors in PDAC cells and xenograft models. Mechanistically, pharmacological inhibition of the MAPK pathway exhibits a double-edged impact on the TRAIL-death receptor axis, transcriptionally upregulating TRAIL yet downregulating its agonistic receptors DR4 and DR5, which may explain the limited therapeutic outcomes of MAPK inhibitors in KRAS-mutant PDAC. Of great interest, tetrandrine stabilizes DR4/DR5 protein via impairing ubiquitination-mediated protein degradation, thereby allowing a synergy with MAPK inhibition in inducing apoptosis in KRAS-mutant PDAC. Our findings identify a new combinatorial approach for treating KRAS-mutant PDAC and highlight the role of TRAIL-DR4/DR5 axis in dictating the therapeutic outcome in KRAS-mutant PDAC.

Application of engineered myoglobins for biosynthesis of clofazimine by integration with chemical synthesis.

Significant efforts have been made in the design of artificial metalloenzymes. Myoglobin (Mb), an O2 carrier, has been engineered to exhibit different functions. Herein, we applied a series of engineered Mb mutants with peroxidase activity for biosynthesis of clofazimine (CFZ), a potential drug with a broad-spectrum antiviral activity, by integration with chemical synthesis. Two of those mutants, F43Y Mb and F43Y/T67R Mb, have been shown to efficiently catalyze the oxidative coupling of 2-N-(4-chlorophenyl) benzene-1,2-diamine (N-4-CPBDA) in the presence of H2O2, with 97% yields. The overall catalytic efficiency (kcat/Km) is 46-fold and 82-fold higher than that of WT Mb, respectively. By further combination of this reaction with chemical synthesis, the production of CFZ was accomplished with an isolated yield of 72%. These results showed that engineered Mbs containing the Tyr-heme cross-link (F43Y Mb and F43Y/T67R Mb) exhibit enhanced activity in the oxidative coupling reaction. This study also indicates that the combination of biocatalysis and chemical synthesis avoids the need for the separation of intermediate products, which offers a convenient approach for the total synthesis of the biological compound CFZ.

Design and Synthesis of Novel Bio-Based Polyester Elastomer with Tunable Oil Resistance.

Polarity determines the oil resistance property of elastomers. In this work, three bio-based polyester elastomers (BPEs) with different mass fraction of ester groups (E) are designed and synthesized aiming to study the relationship of E and oil resistance performance, and to obtain bio-based elastomer materials with tunable oil resistance. Through adjusting the chain length of monomers, E of poly(ethylene glycol/1,3-propanediol/succinate/adipate/itaconate)(PEPSAI), poly(1,3-propanediol/1,4-butanediol/succinate/adipate/itaconate)(PPBSAI), and poly(1,3-propanediol/1,4-butanediol/sebacate/adipate/itaconate)(PPBSeAI) are ≈50.39%, 48.55%, and 39.68%, respectively. Results show that E has great influence on the oil resistance of BPEs. After being immersed in IRM-903# oil for 72 h at room temperature, the changes in mass and volume of BPEs decrease along with the increasing mass fraction of ester groups, indicating improved oil resistance performance. PEPSAI with the highest mass fraction of ester groups presents better oil resistance and lower Tg (better low-temperature resistance) than one of the most used commercial oil-resistant rubber nitrile rubber (N230S). Thus, this work provides a promising strategy to obtain bio-based oil resistant elastomers with practical value.

Sexual mixing patterns in men who have sex with men: network approaches for smart resource allocation.

BACKGROUND: Age-based sexual mixing patterns in men who have sex with men (MSM) can greatly inform strategic allocation of intervention resources to subsets of the population for the purpose of preventing the greatest number of new HIV infections. METHODS: Egocentric network data collected from MSM participating in annual HIV sentinel surveillance surveys were used to assess age-dependent mixing and to explore its epidemiological implications on the risk of HIV transmission risk (among those HIV-infected) and HIV acquisition risk (among those not infected). RESULTS: Mixing in this sample of 1605 Chinese MSM is relatively age assortative (the average of values expressing the degree of preferential mixing were 2.01 in diagonal cells vs 0.87 in off-diagonal cells). Expected numbers of HIV acquisition were highest in the 20-24years age group; those for HIV transmissions were highest among 25-29year olds. The risk of both acquisition and transmission was highest in age groups that immediately follow the most commonly reported ages of sexual debut in this population (i.e. age 20). CONCLUSIONS: These findings suggest that combination prevention resources should be targeted at younger MSM who are at higher risk of both transmission and acquisition. Programs may also do well to target even younger age groups who have not yet debuted in order to establish prevention effects before risky sexual behaviours begin. More research on optimal strategies to access these harder-to-reach subsets of the MSM population is needed. Findings also support ongoing efforts for public health practitioners to collect network data in key populations to support more empirically driven strategies to target prevention resources.

Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study.

INTRODUCTION: Migraine, a prevalent headache disorder with unclear mechanisms and limited treatments, may be influenced by dyslipidemia and genetic factors. Statins and emerging lipid-modifying agents show potential but lack evidence for migraine management. Mendelian Randomization analysis offers insights into causal relationships and therapeutic targets. This study aims to explore genetically predicted lipid traits, drug targets, and their association with migraine risk. METHOD: We conducted Mendelian randomization (MR) analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included HMGCR, PCSK9, NPC1L1, ABCG5/ABCG8, LDLR, LPL, ANGPTL3, APOB, CETP, and APOC3. To determine the effects on migraine risk, we meta-analyzed MR estimates for regional variants using data from two large sample sets. The genetic variants were weighted based on their associations with specific lipid traits, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein A1, and Apolipoprotein B. To obtain association weights, we utilized data from lipid genetics consortia. For lipid-modifying drug targets that exhibited suggestive significance, we further employed expression quantitative trait locus (eQTL) data. Additionally, we performed colocalization analysis to assess genetic confounding. RESULT: The use of genetic proxies for HMGCR inhibition demonstrated a significant association with a decreased risk of migraine in the FinnGen dataset (OR = 0.64, 95% CI: 0.46-0.88, p = 0.0006) and a nearly significant association in the Choquet dataset (OR = 0.78, 95% CI: 0.60-1.01, p = 0.06). When pooling the estimates, the overall effect size showed a reduced risk of migraine (OR = 0.73, 95% CI: 0.60-0.89, p = 0.0016). Similarly, genetic mimicry of LPL enhancement was associated with a lower risk of migraine in the FinnGen dataset (OR = 0.82, 95% CI: 0.69-0.96, p = 0.01) and the Choquet dataset (OR = 0.91, 95% CI: 0.83-0.99, p = 0.03). Pooling the estimates showed a consistent effect size (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding. CONCLUSION: In the study, it was observed that among the 10 lipid-lowering drug targets investigated, LPL and HMGCR showed significant associations with migraine risk. These findings indicate that LPL and HMGCR have the potential to serve as candidate drug targets for the treatment or prevention of migraines.

Financial market sentiment and stock return during the COVID-19 pandemic.

Using 1,287,932 pieces of textual data from news media, we measure the financial market sentiment worldwide. We conduct the first international study of the effect of the financial market sentiment on stock return during the COVID-19 pandemic. Results show that the intensification of the epidemic adversely affects the stock market, but the increasing financial market sentiment increases the stock market return, even during the worst of the pandemic. Our results remain robust using alternative proxies. Additional analysis suggests that negative sentiment has a more significant impact on stock market returns than positive sentiment. Taken together, our findings confirm that negative financial market sentiment amplifies the impact of the crisis on the stock market, and positive financial market sentiment can help mitigate the losses caused by the shock.

Long-Life, High-Rate Rechargeable Lithium Batteries Based on Soluble Bis(2-pyrimidyl) Disulfide Cathode.

Organosulfides are promising candidates as cathode materials for the development of electric vehicles and energy storage systems due to their low-cost and high capacity properties. However, they generally suffer from slow kinetics because of the large rearrangement of S-S bonds and structural degradation upon cycling in batteries. In this paper, we reveal that soluble bis(2-pyrimidyl) disulfide (Pym2 S2 ) can be a high-rate cathode material for rechargeable lithium batteries. Benefiting from the superdelocalization of pyrimidyl group, the extra electrons prefer to be localized on the π* (pyrimidyl group) than σ* (S-S bond) molecular orbitals initially, generating the anion-like intermedia of [Pym2 S2 ]2- and thus decreasing the dissociation energy of the S-S bond. It makes the intrinsic energy barrier of dissociative electron transfer depleted, therefore the lithium half cell exhibits 2000 cycles at 5 C. This study provides a distinct pathway for the design of high-rate, long-cycle-life organic cathode materials.