Publisher Correction: Enhanced strength and ductility in a high-entropy alloy via ordered oxygen complexes.

Change history: In this Letter, owing to a production error, all the data points (except the two points for O-2 and N-2, respectively) were missing in Fig. 1b. The figure has been corrected online.

Alexithymia modulates emotion concept activation during facial expression processing.

Alexithymia is characterized by difficulties in emotional information processing. However, the underlying reasons for emotional processing deficits in alexithymia are not fully understood. The present study aimed to investigate the mechanism underlying emotional deficits in alexithymia. Using the Toronto Alexithymia Scale-20, we recruited college students with high alexithymia (n = 24) or low alexithymia (n = 24) in this study. Participants judged the emotional consistency of facial expressions and contextual sentences while recording their event-related potentials. Behaviorally, the high alexithymia group showed longer response times versus the low alexithymia group in processing facial expressions. The event-related potential results showed that the high alexithymia group had more negative-going N400 amplitudes compared with the low alexithymia group in the incongruent condition. More negative N400 amplitudes are also associated with slower responses to facial expressions. Furthermore, machine learning analyses based on N400 amplitudes could distinguish the high alexithymia group from the low alexithymia group in the incongruent condition. Overall, these findings suggest worse facial emotion perception for the high alexithymia group, potentially due to difficulty in spontaneously activating emotion concepts. Our findings have important implications for the affective science and clinical intervention of alexithymia-related affective disorders.

Advanced Interface Engineering in Gradient Core/Shell Quantum Dots Enables Efficient Photoelectrochemical Hydrogen Evolution.

Semiconductor core/shell quantum dots (QDs) are considered promising building blocks to fabricate photoelectrochemical (PEC) cells for the direct conversion of solar energy into hydrogen (H2). However, the lattice mismatch between core and shell in such QDs results in undesirable defects and severe carrier recombination, limiting photo-induced carrier separation/transfer and solar-to-fuel conversion efficiency. Here, an interface engineering approach is explored to minimize the core-shell lattice mismatch in CdS/CdSexS1-x (x = 0.09-1) core/shell QDs (g-CSG). As a proof-of-concept, PEC cells based on g-CSG QDs yield a remarkable photocurrent density of 13.1 mA cm-2 under AM 1.5 G one-sun illumination (100 mW cm-2), which is ≈54.1% and ≈33.7% higher compared to that in CdS/CdSe0.5S0.5 (g-CSA) and CdS/CdSe QDs (g-CS), respectively. Theoretical calculations and carrier dynamics confirm more efficient carrier separation and charge transfer rate in g-CSG QDs with respect to g-CSA and g-CS QDs. These results are attributed to the minimization of the core-shell lattice mismatch by the cascade gradient shell in g-CSG QDs, which modifies carrier confinement potential and reduces interfacial defects. This work provides fundamental insights into the interface engineering of core/shell QDs and may open up new avenues to boost the performance of PEC cells for H2 evolution and other QDs-based optoelectronic devices.

Neuroblastoma susceptibility and association of N7-methylguanosine modification gene polymorphisms: multi-center case-control study.

BACKGROUND: Neuroblastoma (NB) is a common extracranial solid malignancy in children. The N7-methylguanosine (m7G) modification gene METTL1/WDR4 polymorphisms may serve as promising molecular markers for identifying populations susceptible to NB. METHODS: TaqMan probes was usded to genotype METTL1/WDR4 single nucleotide polymorphisms (SNPs) in 898 NB patients and 1734 healthy controls. A logistic regression model was utilized to calculate the odds ratio (OR) and 95% confidence interval (CI), evaluating the association between genotype polymorphisms and NB susceptibility. The analysis was also stratified by age, sex, tumor origin site, and clinical stage. RESULTS: Individual polymorphism of the METTL1/WDR4 gene investigated in this study did not show significant associations with NB susceptibility. However, combined genotype analysis revealed that carrying all 5 WDR4 protective genotypes was associated with a significantly lower NB risk compared to having 0-4 protective genotypes (AOR = 0.82, 95% CI = 0.69-0.96, P = 0.014). Further stratified analyses revealed that carrying 1-3 METTL1 risk genotypes, the WDR4 rs2156316 CG/GG genotype, the WDR4 rs2248490 CG/GG genotype, and having all five WDR4 protective genotypes were all significantly correlated with NB susceptibility in distinct subpopulations. CONCLUSIONS: In conclusion, our findings suggest significant associations between m7G modification gene METTL1/WDR4 SNPs and NB susceptibility in specific populations. IMPACT: Genetic variation in m7G modification gene is associated with susceptibility to NB. Single nucleotide polymorphisms in METTL1/WDR4 are associated with susceptibility to NB. Single nucleotide polymorphisms of METTL1/WDR4 can be used as a biomarker for screening NB susceptible populations.

Unveiling the role of iPLA2ß in neurodegeneration: From molecular mechanisms to advanced therapies.

Calcium-independent phospholipase A2ß (iPLA2ß), a member of the phospholipase A2 (PLA2s) superfamily, is encoded by the PLA2G6 gene. Mutations in the PLA2G6 gene have been identified as the primary cause of infantile neuroaxonal dystrophy (INAD) and, less commonly, as a contributor to Parkinson's disease (PD). Recent studies have revealed that iPLA2ß deficiency leads to neuroinflammation, iron accumulation, mitochondrial dysfunction, lipid dysregulation, and other pathological changes, forming a complex pathogenic network. These discoveries shed light on potential mechanisms underlying PLA2G6-associated neurodegeneration (PLAN) and offer valuable insights for therapeutic development. This review provides a comprehensive analysis of the fundamental characteristics of iPLA2ß, its association with neurodegeneration, the pathogenic mechanisms involved in PLAN, and potential targets for therapeutic intervention. It offers an overview of the latest advancements in this field, aiming to contribute to ongoing research endeavors and facilitate the development of effective therapies for PLAN.

Enhanced strength and ductility in a high-entropy alloy via ordered oxygen complexes.

Oxygen, one of the most abundant elements on Earth, often forms an undesired interstitial impurity or ceramic phase (such as an oxide particle) in metallic materials. Even when it adds strength, oxygen doping renders metals brittle1-3. Here we show that oxygen can take the form of ordered oxygen complexes, a state in between oxide particles and frequently occurring random interstitials. Unlike traditional interstitial strengthening4,5, such ordered interstitial complexes lead to unprecedented enhancement in both strength and ductility in compositionally complex solid solutions, the so-called high-entropy alloys (HEAs)6-10. The tensile strength is enhanced (by 48.5 ± 1.8 per cent) and ductility is substantially improved (by 95.2 ± 8.1 per cent) when doping a model TiZrHfNb HEA with 2.0 atomic per cent oxygen, thus breaking the long-standing strength-ductility trade-off11. The oxygen complexes are ordered nanoscale regions within the HEA characterized by (O, Zr, Ti)-rich atomic complexes whose formation is promoted by the existence of chemical short-range ordering among some of the substitutional matrix elements in the HEAs. Carbon has been reported to improve strength and ductility simultaneously in face-centred cubic HEAs12, by lowering the stacking fault energy and increasing the lattice friction stress. By contrast, the ordered interstitial complexes described here change the dislocation shear mode from planar slip to wavy slip, and promote double cross-slip and thus dislocation multiplication through the formation of Frank-Read sources (a mechanism explaining the generation of multiple dislocations) during deformation. This ordered interstitial complex-mediated strain-hardening mechanism should be particularly useful in Ti-, Zr- and Hf-containing alloys, in which interstitial elements are highly undesirable owing to their embrittlement effects, and in alloys where tuning the stacking fault energy and exploiting athermal transformations13 do not lead to property enhancement. These results provide insight into the role of interstitial solid solutions and associated ordering strengthening mechanisms in metallic materials.

Impact of sugammadex and neostigmine on outcome after major orthopaedic surgery: A population-based analysis.

BACKGROUND: Residual neuromuscular blockade after surgery remains a major concern given its association with pulmonary complications. However, current clinical practices with and the comparative impact on perioperative risk of various reversal agents remain understudied. OBJECTIVE: We investigated the use of sugammadex and neostigmine in the USA, and their impact on postoperative complications by examining national data. DESIGN: This population-based retrospective study used national Premier Healthcare claims data. SETTING AND PARTICIPANTS: Patients undergoing total hip/knee arthroplasty (THA, TKA), or lumbar spine fusion surgery between 2016 and 2019 in the United States who received neuromuscular blocking agents. INTERVENTION: The effects of sugammadex and neostigmine for pharmacologically enhanced reversal were compared with each other and with controls who received no reversal agent. MAIN OUTCOMES: included pulmonary complications, cardiac complications, and a need for postoperative ventilation. Mixed-effects regression models compared the outcomes between neostigmine, sugammadex, and controls. We report odds ratios (OR) and 95% confidence intervals (CI). Bonferroni-adjusted P values of 0.008 were used to indicate significance. RESULTS: Among 361 553 patients, 74.5% received either sugammadex (20.7%) or neostigmine (53.8%). Sugammadex use increased from 4.4% in 2016 to 35.4% in 2019, whereas neostigmine use decreased from 64.5% in 2016 to 43.4% in 2019. Sugammadex versus neostigmine or controls was associated with significantly reduced odds for cardiac complications (OR 0.86, 95% CI, 0.80 to 0.92 and OR 0.83, 95% CI, 0.78 to 0.89, respectively). Both sugammadex and neostigmine versus controls were associated with reduced odds for pulmonary complications (OR 0.85, 95% CI, 0.77 to 0.94 and OR 0.91, CI 0.85 to 0.98, respectively). A similar pattern of sugammadex and neostigmine was observed for a reduction in severe pulmonary complications, including the requirement of invasive ventilation (OR 0.54, 95% CI, 0.45 to 0.64 and OR 0.53, 95% CI, 0.46 to 0.6, respectively). CONCLUSIONS: Population-based data indicate that sugammadex and neostigmine both appear highly effective in reducing the odds of severe life-threatening pulmonary complications. Sugammadex, especially, was associated with reduced odds of cardiac complications.

Preoperative Evaluation, Anesthetic Considerations, and Perioperative Oral and Parenteral Medications in Total Knee Arthroplasty.

Effective pain management protocol is critical to early mobilization, early discharge, and increasing patient satisfaction for hip and knee arthroplasty. Surgeons have tried to minimize dependence on opioids and opioid-related adverse events through multimodal protocols that use periarticular injections as well as oral and parenteral medications. The efficacy, cost, and adverse effects of each of these components need to be considered when formulating an evidence-based multimodal pain protocol. Recent advancements have changed understanding of the variability in metabolism of commonly given agents around the time of surgery. It is important to provide a systematic approach to the preoperative evaluation, anesthetic considerations, and the administration of oral and parenteral medications routinely used in total knee arthroplasty.

Should Chronological Age be a Consideration in Patients Undergoing Elective Primary Total Knee Arthroplasty?

BACKGROUND: The optimal time for total knee arthroplasty (TKA) requires a balance between patient disability and health state to minimize complications. While chronological age has not been shown to be predictive of complications in elective surgical patients, there is a point beyond which even optimized elderly patients would be at increased risk for complications. The purpose of this study was to examine the impact of chronological age on complications following primary TKA. METHODS: Using an administrative database, the records of 2,129,191 patients undergoing elective unilateral TKA between 2006 and 2021 were reviewed. The primary outcomes of interest were cardiac and pulmonary complications, and their relationship to the Charlson-Deyo Comorbidity Index (CDI) and chronological age. Secondary outcomes included risk of renal, neurologic, infection, and intensive care utilization postoperatively. The results were analyzed using a graphical method. The impact of chronological age as a modifier of overall risk for complications was modeled as a continuous variable. An age cutoff threshold of 80 years was also assigned for clinical convenience. RESULTS: The risk of complications correlated more closely to the CDI (odds ratio (OR) 1.37 to 2.1) than chronological age (OR 1.0 to 1.1) across the various complications [Table 1. However, beyond age 80 years, the risks of cardiac, pulmonary, renal, and cerebrovascular complications were significantly increased for all CDI categories (OR 1.73 to 3.40) compared to patients below age 80 years [Table 2] [Figures 1A and 1B]. CONCLUSIONS: Chronologic age can impact the risk of complications even in well-optimized elderly patients undergoing primary TKA. As arthroplasty continues to transition to outpatient settings and inpatient denials increase, these results can help patients, physicians, and payors mitigate risk while optimizing the allocation of resources.

Palladium-Catalyzed Cascade Heck Coupling and Allylboration of Iododiboron Compounds via Diboryl Radicals.

Geminal bis(boronates) are versatile synthetic building blocks in organic chemistry. The fact that they predominantly serve as nucleophiles in the previous reports, however, has restrained their synthetic potential. Herein we disclose the ambiphilic reactivity of α-halogenated geminal bis(boronates), of which the first catalytic utilization was accomplished by merging a formal Heck cross-coupling with a highly diastereoselective allylboration of aldehydes or imines, providing a new avenue for rapid assembly of polyfunctionalized boron-containing compounds. We demonstrated that this cascade reaction is highly efficient and compatible with various functional groups, and a wide range of heterocycles. In contrast to a classical Pd(0/II) scenario, mechanistic experiments and DFT calculations have provided strong evidence for a catalytic cycle involving Pd(I)/diboryl carbon radical intermediates.

Evidence-based Perioperative Practice Utilization among Various Racial Populations-A Retrospective Cohort Trending Analysis of Lower Extremity Total Joint Arthroplasty Patients.

BACKGROUND: Various studies have demonstrated racial disparities in perioperative care and outcomes. The authors hypothesize that among lower extremity total joint arthroplasty patients, evidence-based perioperative practice utilization increased over time among all racial groups, and that standardized evidence-based perioperative practice care protocols resulted in reduction of racial disparities and improved outcomes. METHODS: The study analyzed 3,356,805 lower extremity total joint arthroplasty patients from the Premier Healthcare database (Premier Healthcare Solutions, Inc., USA). The exposure of interest was race (White, Black, Asian, other). Outcomes were evidence-based perioperative practice adherence (eight individual care components; more than 80% of these implemented was defined as "high evidence-based perioperative practice"), any major complication (including acute renal failure, delirium, myocardial infarction, pulmonary embolism, respiratory failure, stroke, or in-hospital mortality), in-hospital mortality, and prolonged length of stay. RESULTS: Evidence-based perioperative practice adherence rate has increased over time and was associated with reduced complications across all racial groups. However, utilization among Black patients was below that for White patients between 2006 and 2021 (odds ratio, 0.94 [95% CI, 0.93 to 0.95]; 45.50% vs. 47.90% on average). Independent of whether evidence-based perioperative practice components were applied, Black patients exhibited higher odds of major complications (1.61 [95% CI, 1.55 to 1.67] with high evidence-based perioperative practice; 1.43 [95% CI, 1.39 to 1.48] without high evidence-based perioperative practice), mortality (1.70 [95% CI, 1.29 to 2.25] with high evidence-based perioperative practice; 1.29 [95% CI, 1.10 to 1.51] without high evidence-based perioperative practice), and prolonged length of stay (1.45 [95% CI, 1.42 to 1.48] with high evidence-based perioperative practice; 1.38 [95% CI, 1.37 to 1.40] without high evidence-based perioperative practice) compared to White patients. CONCLUSIONS: Evidence-based perioperative practice utilization in lower extremity joint arthroplasty has been increasing during the last decade. However, racial disparities still exist with Black patients consistently having lower odds of evidence-based perioperative practice adherence. Black patients (compared to the White patients) exhibited higher odds of composite major complications, mortality, and prolonged length of stay, independent of evidence-based perioperative practice use, suggesting that evidence-based perioperative practice did not impact racial disparities regarding particularly the Black patients in this surgical cohort.

Effectiveness of oral versus intravenous tranexamic acid in primary total hip and knee arthroplasty: a randomised, non-inferiority trial.

BACKGROUND: Tranexamic acid (TXA) reduces rates of blood transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the use of oral TXA rather than intravenous (i.v.) TXA might improve safety and reduce cost, it is not clear whether oral administration is as effective. METHODS: This noninferiority trial randomly assigned consecutive patients undergoing primary THA or TKA under neuraxial anaesthesia to either one preoperative dose of oral TXA or one preoperative dose of i.v. TXA. The primary outcome was calculated blood loss on postoperative day 1. Secondary outcomes were transfusions and complications within 30 days of surgery. RESULTS: Four hundred participants were randomised (200 THA and 200 TKA). The final analysis included 196 THA patients (98 oral, 98 i.v.) and 191 TKA patients (93 oral, 98 i.v.). Oral TXA was non-inferior to i.v. TXA in terms of calculated blood loss for both THA (effect size=-18.2 ml; 95% confidence interval [CI], -113 to 76.3; P<0.001) and TKA (effect size=-79.7 ml; 95% CI, -178.9 to 19.6; P<0.001). One patient in the i.v. TXA group received a postoperative transfusion. Complication rates were similar between the two groups (5/191 [2.6%] oral vs 5/196 [2.6%] i.v.; P=1.00). CONCLUSIONS: Oral TXA can be administered in the preoperative setting before THA or TKA and performs similarly to i.v. TXA with respect to blood loss and transfusion rates. Switching from i.v. to oral TXA in this setting has the potential to improve patient safety and decrease costs.

Neuraxial Use Among Total Knee and Hip Arthroplasty Patients With Multiple Sclerosis or Myasthenia Gravis.

BACKGROUND: Surgical patients with preexisting neurological diseases create greater challenges to perioperative management, and choice of anesthetic is often complicated. We investigated neuraxial anesthesia use in total knee and hip arthroplasty (TKA/THA) recipients with multiple sclerosis or myasthenia gravis compared to the general population. METHODS: We retrospectively analyzed patients undergoing a TKA/THA with a diagnosis of multiple sclerosis or myasthenia gravis (Premier Health Database, 2006-2019). The primary outcome was neuraxial anesthesia use in multiple sclerosis or myasthenia gravis patients compared to the general population. Secondary outcomes were length of stay, intensive care unit admission, and mechanical ventilation. We measured the association between the aforementioned subgroups and neuraxial anesthesia use. Subsequently, subgroup-specific associations between neuraxial anesthesia and secondary outcomes were measured. We report odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 2,184,193 TKA/THAs, 7559 and 3176 had a multiple sclerosis or myasthenia gravis diagnosis, respectively. Compared to the general population, neuraxial anesthesia use was lower in multiple sclerosis patients (OR, 0.61; CI, 0.57-0.65; P < .0001) and no different in myasthenia gravis patients (OR, 1.05; CI, 0.96-1.14; P = .304). Multiple sclerosis patients administered neuraxial anesthesia (compared to those without neuraxial anesthesia) had lower odds of prolonged length of stay (OR, 0.63; CI, 0.53-0.76; P < .0001) mirroring neuraxial anesthesia benefits seen in the general population. CONCLUSIONS: Neuraxial anesthesia use was lower in surgical patients with multiple sclerosis compared to the general population but no different in those with myasthenia gravis. Neuraxial use was associated with lower odds of prolonged length of stay.

Association between GPC2 polymorphisms and neuroblastoma risk in Chinese children.

BACKGROUND: The cell surface glycoprotein glypican 2 (GPC2) has been shown to increase susceptibility to neuroblastoma, which is the most common malignancy in children. However, associations between single nucleotide polymorphism(s) of GPC2 and neuroblastoma risk remain unclarified. METHODS: We conducted a case-control study to investigate two GPC2 polymorphisms (rs1918353 G>A and rs7799441 C>T) in 473 healthy controls and 402 pediatric patients with neuroblastoma. Single nucleotide polymorphism (SNP) genotyping was conducted on the samples by the TaqMan technique, and the data were subsequently analyzed by the t test, chi-squared test, and logistic regression model. In addition, we further performed stratification analysis by age, sex, tumor site of origin, or clinical stage to control confounding factors. RESULTS: According to the data of dominant models (GA/AA vs. GG: adjusted OR = 0.99, 95% CI = 0.76-1.29, p = 0.943; CT/TT vs. CC: adjusted OR = 0.91, 95% CI = 0.70-1.19, p = 0.498) or other comparisons, as well as the conjoint analysis (adjusted OR = 1.22, 95% CI = 0.93-1.59, p = 0.152), we unfortunately proved that the analysis of single or multiple loci did not support any significant association of GPC2 polymorphisms with susceptibility to neuroblastoma. CONCLUSION: GPC2 polymorphisms (rs1918353 G>A and rs7799441 C>T) are unable to statistically affect neuroblastoma risk in Chinese children. Therefore, more samples, especially from patients of various ethnic backgrounds, are required to increase the sample size and verify the effect of GPC2 polymorphisms on neuroblastoma risk in the presence of ethnic factor.

Trends in use, outcomes, and revision procedures of anterior cervical disc replacement in the United States: a premiere database analysis from 2006-2019.

PURPOSE: We sought to characterize trends in demographics, comorbidities, and postoperative complications among patients undergoing primary and revision cervical disc replacement (pCDR/rCDR) procedures. METHODS: In this retrospective database study, the Premier Healthcare database was queried from 2006 to 2019. Annual proportions or medians were calculated for patient and hospital characteristics, comorbidities, and postoperative complications associated with CDR surgery. Trends were assessed using linear regression analyses with year of service as the sole predictor. RESULTS: A total of 16,178 pCDR and 758 rCDR cases were identified, with a median (IQR) age of 46 (39; 53) and 51 (43; 60) years among patients, respectively. The annual number of both procedures increased between 2006 and 2019, from 135 to 2220 for pCDR (p < 0.001), and from 17 to 49 for rCDR procedures (p < 0.001), with radiculopathy being the main indication for surgery in both groups. Mechanical failure was identified as a major indication for rCDR procedures with an increase over time (p = 0.002). Baseline patient comorbidity burden (p = 0.045) and complication rates (p < 0.001) showed an increase. For both procedures, an increase in outpatient surgeries and procedures performed in rural hospitals was seen (pCDR: p = 0.045; p = 0.006; rCDR: p = 0.028; p = 0.034). CONCLUSION: PCDR and rCDR procedures significantly increased from 2006 to 2019. At the same time, comorbidity burden and complication rates increased, while procedures were more often performed in an outpatient and rural setting. The identification of these trends can help guide future practice and lead to further areas of research.

Sintering Behaviors of Supported Nanoparticles Related to Spatial Location by a Quasi-Four-Dimensional TEM.

The performance degradation via sintering phenomenon is a critical issue for the application of supported nanoparticles in industrial catalysis. However, the challenges to combine in situ stimulation and three-dimensional (3D) characterization hinder a profound understanding of sintering behaviors, thus the effect of spatial location on nanoparticles sintering has long been neglected. Herein, based on a homemade holder integrated with in situ Joule heating and electron tomography, a quasi-four-dimensional (4D) transmission electron microscope characterization approach is developed to reveal the spatial location of supported nanoparticles and its pronounced impact on size distribution and sintering behaviors. The results of 3D visualization and statistical analysis demonstrate a strong location-dependent sintering behavior of supported nanoparticles, where external nanoparticles sinter via migration coalescence, and internal nanoparticles sinter via Ostwald ripening. The quasi-4D methods developed in this work can also be extended to the study on 3D configuration evolution of other nanomaterials under an external stimulus.

Early versus deferred endovenous sclerotherapy of superficial venous reflux in patients with venous ulceration.

This study aimed to compare early endovenous sclerotherapy with superficial venous reflux combined with compression therapy and deferred intervention in patients with venous leg ulcers (VLUs). A total of 80 patients with 80 VLUs treated at the Department of General Surgery, Shangjin Nanfu Hospital, Chengdu, China, between February 2022 and January 2023 were included in the study. The primary outcome was the time to ulcer healing from the date of compression therapy or endovenous sclerotherapy. Secondary outcome measures were the rate of ulcer healing at 6 months, the rate of ulcer recurrence at 6 months, and patient-reported health-related quality of life. A total of 54 patients received early intervention and 26 received deferred intervention. The patient and clinical characteristics at baseline were similar between the two treatment groups. The median time to ulcer healing was 1.5 months (95% confidence interval [CI], 1.3-1.7 months) in the early-intervention group and 3.5 months (95% CI, 2.9-4.1 months) in the deferred-intervention group. The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group (p < 0.001). The rate of ulcer healing at 6 months was 94% in the early-intervention group and 92% in the deferred-intervention group. The rate of ulcer recurrence before the end of the 6-month follow-up period was 2% in the early-intervention group and 4% in the deferred-intervention group. In conclusion, early endovenous sclerotherapy for superficial venous reflux resulted in faster healing of VLUs than deferred endovenous sclerotherapy.

Comparing Long-Term Prognosis in Chronic Critically Ill Patients: A Case Series Study of Medical versus Surgical Sepsis.

Background and Objectives: Chronic critical illness (CCI) is a syndrome characterized by persistent organ dysfunction that requires critical care therapy for ≥14 days. Sepsis and respiratory failure constitute the two primary causes of CCI. A better understanding of this patient population and their clinical course may help to risk-stratify them early during hospitalization. Our objective was to identify whether the source of sepsis (medical versus surgical) affected clinical trajectory and prognosis in patients developing CCI. Materials and Methods: We describe a cohort of patients having acute respiratory failure and sepsis and requiring critical care therapy in the medical (MICU) or surgical (SICU) critical care units for ≥14 days. Given the relative infrequency of CCI, we use a case series design to examine mortality, functional status, and place of residence (home versus non-home) at one year following their index hospitalization. Results: In medical patients developing CCI (n = 31), the severity of initial organ dysfunction, by SOFA score, was significantly associated with the development of CCI (p = 0.002). Surgical patients with CCI (n = 7) experienced significantly more ventilator-free days within the first 30 days following sepsis onset (p = 0.004), as well as less organ dysfunction at day 14 post-sepsis (p < 0.0001). However, one-year mortality, one-year functional status, and residency at home were not statistically different between cohorts. Moreover, 57% of surgical patients and 26% of medical patients who developed CCI were living at home for one year following their index hospitalization (p = 0.11). Conclusions: While surgical patients who develop sepsis-related CCI experience more favorable 30-day outcomes as compared with medical patients, long-term outcomes do not differ significantly between groups. This suggests that reversing established organ dysfunction and functional disability, regardless of etiology, is more challenging compared to preventing these complications at an earlier stage.

Regulating the Sequence Structure of Conjugated Block Copolymers Enables Large-Area Single-Component Organic Solar Cells with High Efficiency and Stability.

Single-component organic solar cells (SCOSCs) based on conjugated block copolymers (CBCs) by covalently bonding a polymer donor and polymer acceptor become more and more appealing due to the formation of a favorable and stable morphology. Unfortunately, a deep understanding of the effect of the assembly behavior caused by the sequence structure of CBCs on the device performance is still missing. Herein, from the aspect of manipulating the sequence length and distribution regularity of CBCs, we synthesized a series of new CBCs, namely D18(20)-b-PYIT, D18(40)-b-PYIT and D18(60)-b-PYIT by two-pot polymerization, and D18(40)-b-PYIT(r) by traditional one-pot method. It is observed that precise manipulation of sequence length and distribution regularity of the polymer blocks fine-tunes the self-assembly of the CBCs, optimizes film morphology, improves optoelectronic properties, and reduces energy loss, leading to simultaneously improved efficiency and stability. Among these CBCs, the D18(40)-b-PYIT-based device achieves a high efficiency of 13.4 % with enhanced stability, which is an outstanding performance among SCOSCs. Importantly, the regular sequence distribution and suitable sequence length of the CBCs enable a facile film-forming process of the printed device. For the first time, the blade-coated large-area rigid/flexible SCOSCs are fabricated, delivering an impressive efficiency of 11.62 %/10.73 %, much higher than their corresponding binary devices.

Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression.

Objective: AlkB homolog 5 (ALKBH5) has been proven to be closely related to tumors. However, the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported. Methods: The potential functional single-nucleotide polymorphisms (SNPs) in ALKBH5 were identified by National Center for Biotechnology Information (NCBI) dbSNP screening and SNPinfo software. TaqMan probes were used for genotyping. A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma. The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry (IHC). Cell counting kit-8 (CCK-8), plate colony formation and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to compare cell migration and invasion. Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism. RNA sequencing, N6-methyladenosine (m6A) sequencing, m6A methylated RNA immunoprecipitation (MeRIP) and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1. Results: ALKBH5 was highly expressed in neuroblastoma. Knocking down ALKBH5 inhibited the proliferation, migration and invasion of cancer cells. miR-186-3p negatively regulates the expression of ALKBH5, and this ability is affected by the rs8400 polymorphism. When the G nucleotide was mutated to A, the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased, resulting in upregulation of ALKBH5. SPP1 is the downstream target gene of the ALKBH5 oncogene. Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma. Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma. Conclusions: We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms. The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis.