Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study.

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

A novel non-invasive embryo evaluation method (NICS-Timelapse) with enhanced predictive precision and clinical impact.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

Intratumoral delivery of the chitin-derived C100 adjuvant promotes robust STING, IFNAR, and CD8+ T cell-dependent anti-tumor immunity.

Stimulator of IFN genes (STING) is a promising target for adjuvants utilized in in situ cancer vaccination approaches. However, key barriers remain for clinical translation, including low cellular uptake and accessibility, STING variability necessitating personalized STING agonists, and interferon (IFN)-independent signals that can promote tumor growth. Here, we identify C100, a highly deacetylated chitin-derived polymer (HDCP), as an attractive alternative to conventional STING agonists. C100 promotes potent anti-tumor immune responses, outperforming less deacetylated HDCPs, with therapeutic efficacy dependent on STING and IFN alpha/beta receptor (IFNAR) signaling and CD8+ T cell mediators. Additionally, C100 injection synergizes with systemic checkpoint blockade targeting PD-1. Mechanistically, C100 triggers mitochondrial stress and DNA damage to exclusively activate the IFN arm of the cGAS-STING signaling pathway and elicit sustained IFNAR signaling. Altogether, these results reveal an effective STING- and IFNAR-dependent adjuvant for in situ cancer vaccines with a defined mechanism and distinct properties that overcome common limitations of existing STING therapeutics.

Loss of function variant in CIP2A associated with female infertility with early embryonic arrest and fragmentation.

BACKGROUND: Early embryonic arrest and fragmentation (EEAF) is a common cause of female infertility, but the genetic causes remain to be largely unknown. CIP2A encodes the cellular inhibitor of PP2A, playing a crucial role in mitosis and mouse oocyte meiosis. METHODS: Exome sequencing and Sanger sequencing were performed to identify candidate causative genes in patients with EEAF. The pathogenicity of the CIP2A variant was assessed and confirmed in cultured cell lines and human oocytes through Western blotting, semi-quantitative RT-PCR, TUNEL staining, and fluorescence localization analysis. FINDINGS: We identified CIP2A (c.1510C > T, p.L504F) as a novel candidate disease-causing gene in human EEAF from a consanguineous family. L504 is highly conserved throughout evolution. The CIP2A variant (c.1510C > T, p.L504F) reduced the expression level of the mutant CIP2A protein, leading to the abnormal aggregation of mutant CIP2A protein and cell apoptosis. Abnormal aggregation of CIP2A protein and chromosomal dispersion occurred in the patient's oocytes and early embryos. We further replicated the patient phenotype by knockdown CIP2A in human oocytes. Additionally, CIP2A deficiency resulted in decreased levels of phosphorylated ERK1/2. INTERPRETATION: We first found that the CIP2A loss-of-function variant associate with female infertility characterized by EEAF. Our findings suggest the uniqueness and importance of CIP2A gene in human oocyte and early embryo development. FUNDING: This work was supported by National Key Research and Development Program of China (2023YFC2706302), the National Natural Science Foundation of China (81000079, 81170165, and 81870959), the HUST Academic Frontier Youth Team (2016QYTD02), and the Key Research of Huazhong University of Science and Technology, Tongji Hospital (2022A20).

Chromium levels in placental tissue and neural tube defects: Association and mechanistic study.

Human exposure to chromium (Cr) is common but little is known about its adverse effects on pregnancy outcomes. This study aimed to explore the association between Cr exposure and the risk of neural tube defects (NTDs) and the underlying mechanisms of Cr-induced NTDs. 593 controls and 408 NTD cases with placentas were included in this study. Chromium trichloride (Cr(III)) and potassium dichromate (Cr(VI)) were intragastrically administered to pregnant mice and the number of NTDs was recorded. The odds ratio for total NTDs in the highest exposure group in placenta was 4.18 (95% confidence interval (CI), 1.97-8.84). The incidence of fetal NTDs in mice administered with Cr(III) showed a dose-response relationship. Cr(VI) didn't show teratogenicity of NTDs whereas increased the stillbirth rate. Prenatal exposure to Cr(III) increased levels of oxidative stress and apoptosis in fetal mice. RNA-sequencing results indicated significant enrichment of the MAPK pathway. RT-qPCR and Western blot analysis revealed that Cr(III) induced increased expression of p-JNK, p-P38, and Casp3. Toxicological effects can be partly antagonized by antioxidant supplementation. High chromium exposure was associated with increased human NTD risks. Excessive Cr(III) exposure can induce NTDs in fetal mice by increasing apoptosis through upgrading oxidative stress and then activating JNK/P38 MAPK signaling pathway.

Organic-inorganic hybrid interfaces with π-d electron coupling for preventing metal and sulfur leaching toward enhanced oxygen evolution reaction.

Transition metal sulfides (TMSs) catalysts with high catalytic oxygen evolution reaction (OER) activity have been extensively studied, especially Fe and Co-based sulfides. Fe and Co active sites with a strong synergistic effect, which can adjust the electron density distribution and effectively improve the electrocatalytic OER activity. However, TMSs have poor stability in alkaline environment caused by metal ions and sulfur elements are facilitated to dissolve. In this work, TMSs was modified by polyaniline (PANI) to inhibit the precipitation of iron, cobalt, and sulfur elements and enhance its stability under alkaline conditions. Moreover, π-d structure can also be formed by the coating of PANI, which can further adjust its own electronic structure on the basis of stabilizing the TMSs structure, so as to improve the electrochemical performance, rendering them to stably operate at harsh environment for more than 90 h. These findings offer new guidance for improving the electrocatalytic stability of TMSs.

Kinetic pathway of HIV-1 TAR cotranscriptional folding.

The Trans-Activator Receptor (TAR) RNA, located at the 5'-end untranslated region (5' UTR) of the human immunodeficiency virus type 1 (HIV-1), is pivotal in the virus's life cycle. As the initial functional domain, it folds during the transcription of viral mRNA. Although TAR's role in recruiting the Tat protein for trans-activation is established, the detailed kinetic mechanisms at play during early transcription, especially at points of temporary transcriptional pausing, remain elusive. Moreover, the precise physical processes of transcriptional pause and subsequent escape are not fully elucidated. This study focuses on the folding kinetics of TAR and the biological implications by integrating computer simulations of RNA folding during transcription with nuclear magnetic resonance (NMR) spectroscopy data. The findings reveal insights into the folding mechanism of a non-native intermediate that triggers transcriptional pause, along with different folding pathways leading to transcriptional pause and readthrough. The profiling of the cotranscriptional folding pathway and identification of kinetic structural intermediates reveal a novel mechanism for viral transcriptional regulation, which could pave the way for new antiviral drug designs targeting kinetic cotranscriptional folding pathways in viral RNAs.

Dietary Knowledge and Preference Among Middle-Aged and Older Chinese Couples.

This study investigates the interdependence of dietary knowledge and preference and potential rural-urban differences among middle-aged and older Chinese couples. Couple-level data from the 2015 China Health and Nutrition Survey were included (N = 2933). Structural Equation Model examined the actor and partner effects of dietary knowledge on dietary preferences. Findings indicated that greater dietary knowledge was associated with one's healthier diet preferences among both rural and urban residents (P < .01). In rural areas, ones' dietary knowledge was associated with their partners' dietary preferences (P < .01). However, in urban areas, husbands' dietary knowledge was not associated with their wives' dietary preferences (P = .58), whereas wives' dietary knowledge was associated with their husbands' dietary preferences (P < .05). The rural-urban difference indicates the greater decision-making power of men in rural households. A couple-based approach is suggested for dietary interventions and guidelines promoting healthy eating in China, particularly in rural regions.

Shift in microorganism and functional gene abundance during completely autotrophic nitrogen removal over nitrite (CANON) process.

Nitrification-denitrification process has failed to meet wastewater treatment standards. The completely autotrophic nitrite removal (CANON) process has a huge advantage in the field of low carbon/nitrogen wastewater nitrogen removal. However, slow start-up and system instability limit its applications. In this study, the time of the start-up CANON process was reduced by using bio-rope as loading materials. The establishing of graded dissolved oxygen improved the stability of the CANON process and enhanced the stratification effect between functional microorganisms. Microbial community structure and the abundance of nitrogen removal functional genes are also analyzed. The results showed that the CANON process was initiated within 75 days in the complete absence of anaerobic ammonium oxidizing bacteria (AnAOB) inoculation. The ammonium and nitrogen removal efficiencies of CANON process reached to 94.45% and 80.76% respectively. The results also showed that the relative abundance of nitrogen removal bacterial in the biofilm gradually increases with the dissolved oxygen content in the solution decreases. In contrast, the relative abundance of ammonia oxidizing bacteria was positively correlated with the dissolved oxygen content in the solution. The relative abundance of g__Candidatus_Brocadia in biofilm was 15.56%, and while g__Nitrosomonas was just 0.6613%. Metagenomic analysis showed that g__Candidatus_Brocadia also contributes 66.37% to the partial-nitrification functional gene Hao (K10535). This study presented a new idea for the cooperation between partial-nitrification and anammox, which improved the nitrogen removal system stability.

A new insight on evaluation of the fertility and pregnancy outcome in patients with primary Sjögren syndrome: a propensity score matched study in multi-IVF centers.

BACKGROUND: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. OBJECTIVE: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. METHODS: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. RESULTS: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. CONCLUSION: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.

Decreased embryo developmental potential and lower cumulative pregnancy rate in men with multiple morphological abnormalities of the sperm flagella.

Objective: Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of asthenoteratozoospermia. Previous studies have reported a comparable intracytoplasmic sperm injection (ICSI) outcome in terms of fertilization rate and clinical pregnancy rate in patients with MMAF compared with those with no MMAF; however, others have conflicting opinions. Assisted reproductive technology (ART) outcomes in individuals with MMAF are still controversial and open to debate. Methods: A total of 38 patients with MMAF treated at an academic reproductive center between January 2014 and July 2022 were evaluated in the current retrospective cohort study and followed up until January 2023. Propensity score matching was used to adjust for the baseline clinical characteristics of the patients and to create a comparable control group. The genetic pathogenesis of MMAF was confirmed by whole exome sequencing. The main outcomes were the embryo developmental potential, the cumulative pregnancy rate (CLPR), and the cumulative live birth rate (CLBR). Results: Pathogenic variants in known genes of DNAH1, DNAH11, CFAP43, FSIP2, and SPEF2 were identified in patients with MMAF. Laboratory outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyst rate, followed a trend of decline in the MMAF group (p < 0.05). Moreover, according to the embryo transfer times and complete cycles, the CLPR in the cohort of MMAF was lower compared with the oligoasthenospermia pool (p = 0.033 and p = 0.020, respectively), while no statistical differences were observed in the neonatal outcomes. Conclusion: The current study presented decreased embryo developmental potential and compromised clinical outcomes in the MMAF cohort. These findings may provide clinicians with evidence to support genetic counseling and clinical guidance in specific patients with MMAF.

Machine learning-inferred and energy landscape-guided analyses reveal kinetic determinants of CRISPR/Cas9 gene editing.

The CRISPR/Cas nucleases system is widely considered the most important tool in genome engineering. However, current methods for predicting on/off-target effects and designing guide RNA (gRNA) rely on purely data-driven approaches or focus solely on the system's thermal equilibrium properties. Nonetheless, experimental evidence suggests that the process is kinetically controlled rather than being in equilibrium. In this study, we utilized a vast amount of available data and combined random forest, a supervised ensemble learning algorithm, and free energy landscape analysis to investigate the kinetic pathways of R-loop formation in the CRISPR/Cas9 system and the intricate molecular interactions between DNA and the Cas9 RuvC and HNH domains. The study revealed (a) a novel three-state kinetic mechanism, (b) the unfolding of the activation state of the R-loop being the most crucial kinetic determinant and the key predictor for on- and off-target cleavage efficiencies, and (c) the nucleotides from positions +13 to +16 being the kinetically critical nucleotides. The results provide a biophysical rationale for the design of a kinetic strategy for enhancing CRISPR/Cas9 gene editing accuracy and efficiency.

Fertility history and intentions of married women, China.

Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.

Inadvertent antibiotic exposure during pregnancy may increase the risk for neural tube defects in offspring.

BACKGROUND: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. METHODS: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. RESULTS: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01-10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. CONCLUSIONS: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

Mechanism Insights into the Enantioselective Bioactivity and Fumonisin Biosynthesis of Mefentrifluconazole to Fusarium verticillioides.

The occurrence of maize ear rot caused by Fusarium verticillioides (F. verticillioides) poses a threat to the yield and quality of maize. Mefentrifluconazole enantiomers appear to have strong stereoselective activity against F. verticillioides and cause differences in fumonisin production. We evaluated the stereoselective activity of mefentrifluconazole enantiomers by determining inhibition of the strain, hyphae, and conidia. Strain inhibition by R-(-)-mefentrifluconazole was 241 times higher than S-(+)-mefentrifluconazole and 376 times higher in conidia inhibition. For the mechanism of the enantioselective bioactivity, R-mefentrifluconazole had stronger binding to proteins than S-(+)-mefentrifluconazole. Under several concentration conditions, the fumonisin concentration was 1.3-24.9-fold higher in the R-(-)-mefentrifluconazole treatment than in the S-(+)-mefentrifluconazole treatment. The R-enantiomer stimulated fumonisin despite a higher bioactivity. As the incubation time increased, the stimulation of the enantiomers on fumonisin production decreased. R-(-)-Mefentrifluconazole stimulated higher fumonisin production in F. verticillioides at 25 °C compared to 30 °C. This study established a foundation for the development of high-efficiency and low-risk pesticides.

p97 inhibits integrated stress response-induced neuronal apoptosis after subarachnoid hemorrhage in mice by enhancing proteasome function.

Neuronal apoptosis is a common pathological change in early brain injury after subarachnoid hemorrhage (SAH), and it is closely associated with neurological deficits. According to previous research, p97 exhibits a remarkable anti-cardiomyocyte apoptosis effect. p97 is a critical molecule in the growth and development of the nervous system. However, it remains unknown whether p97 can exert an anti-neuronal apoptosis effect in SAH. In the present study, we examined the role of p97 in neuronal apoptosis induced after SAH and investigated the underlying mechanism. We established an in vivo SAH mice model and overexpressed the p97 protein through transfection of the mouse cerebral cortex. We analyzed the protective effect of p97 on neurons and evaluated short-term and long-term neurobehavior in mice after SAH. p97 was found to be significantly downregulated in the cerebral cortex of the affected side in mice after SAH. The site showing reduced p97 expression also exhibited a high level of neuronal apoptosis. Adeno-associated virus-mediated overexpression of p97 significantly reduced the extent of neuronal apoptosis, improved early and long-term neurological function, and repaired the neuronal damage in the long term. These neuroprotective effects were accompanied by enhanced proteasome function and inhibition of the integrated stress response (ISR) apoptotic pathway involving eIF2α/CHOP. The administration of the p97 inhibitor NMS-873 induced a contradictory effect. Subsequently, we observed that inhibiting the function of the proteasome with the proteasome inhibitor PS-341 blocked the anti-neuronal apoptosis effect of p97 and enhanced the activation of the ISR apoptotic pathway. However, the detrimental effects of NMS-873 and PS-341 in mice with SAH were mitigated by the administration of the ISR inhibitor ISRIB. These results suggest that p97 can promote neuronal survival and improve neurological function in mice after SAH. The anti-neuronal apoptosis effect of p97 is achieved by enhancing proteasome function and inhibiting the overactivation of the ISR apoptotic pathway.

Characteristics, predictors and outcomes of new-onset QT prolongation in sepsis: a multicenter retrospective study.

BACKGROUND: Sepsis-induced myocardial injury is a serious complication of sepsis. QT prolongation is a proarrhythmic state which reflects myocardial injury in a group of heterogeneous disorders. However, the study on the clinical value of QT prolongation in sepsis is limited. METHODS: We aimed to investigate the clinical characteristics and predictors of new-onset QT prolongation in sepsis and its impact on the outcome in a multicenter retrospective cohort study. Electrocardiographic and clinical data were collected from patients with sepsis from the wards and intensive care units of four centers after exclusion of QT-influencing medications and electrolyte abnormalities. Clinical outcomes were compared between patients with and without QT prolongation (QTc > 450 ms). Multivariate analysis was performed to ascertain whether QT prolongation was an independent predictor for 30-day mortality. The factors predicting QT prolongation in sepsis were also analyzed. RESULTS: New-onset QT prolongation occurred in 235/1024 (22.9%) patients. The majority demonstrated similar pattern as type 1 long QT syndrome. Patients with QT prolongation had a higher 30-day in-hospital mortality (P < 0.001), which was also associated with increased tachyarrhythmias including paroxysmal atrial fibrillation or tachycardia (P < 0.001) and ventricular arrhythmia (P < 0.001) during hospitalization. QT prolongation independently predicted 30-day mortality (P = 0.044) after multivariate analysis. History of coronary artery disease (P = 0.001), septic shock (P = 0.008), acute respiratory (P < 0.001), heart (P = 0.021) and renal dysfunction (P = 0.013) were independent predictors of QT prolongation in sepsis. CONCLUSIONS: New-onset QT prolongation in sepsis was associated with increased mortality as well as atrial and ventricular arrhythmias, which was predicted by disease severity and organ dysfunction.

Heritage and hesitancy: how preference for traditional Chinese medicine influences vaccine attitudes.

Introduction: Vaccine hesitancy, amplified by the COVID-19 pandemic, is a pressing public health challenge. This study investigates the association between Traditional Chinese Medicine (TCM) preference and COVID-19 vaccine hesitancy within China. Methods: The study uses data from the 2021 Chinese General Social Survey (CGSS) (N = 2,690). Logistic regressions and Karlson-Holm-Breen (KHB) method are employed to analyzed the relationship between TCM preference and vaccine hesitancy. Results: The study reaffirms prior findings by revealing a robust and stable association between TCM preference and vaccine hesitancy, which remains unaffected by socioeconomic and demographic confounders, as well as institutional trust dynamics of healthcare system. Contrary to expectations, TCM enthusiasts do not exhibit vaccine hesitancy based on divergent epistemological views concerning vaccine risks and immunity acquisition compared to biomedicine. Discussion: This research enriches understandings of the intricate relations between healthcare paradigms and vaccine attitudes, inviting further inquiry into the role of CAM in shaping vaccination behaviors across different cultures and contexts. The insights bear significant public health implications for enhancing vaccine acceptance and coverage, particularly among populations where CAM practices wield substantial influence.

MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. SIGNIFICANCE: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.

Electride pureα-Zr: interstitial electrons induced type-II nodal line.

Electrides have attracted significant attention in the fields of physics, materials science, and chemistry due to their distinctive electron properties characterized by weak nuclear binding. In this study, based on first-principles calculations and symmetry analysis, we report that the pure zirconium with alpha-phase (α-Zr) is expected to be the electrically neutral electride with topological nodal loop. Furthermore, the nodal loop located at thekz= 0 plane exhibits a clear drumhead-like surface state. The energy levels of the topological nodal loop can be regulated by applying uniaxial strain, resulting in the topological nodal loop being closer to the Fermi level. Remarkably, the work function of the electride Zr shows a significant anisotropy along the (001), (100), and (110) directions, particularly with a low work function of 3.14 eV along the (110) surface. Therefore, we predict thatα-Zr provides a promising platform for future research on topological electrides.