Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. The spatial architecture of cell types and gene expression are the basis of cell-cell interactions, biological function and disease pathology, but are not well investigated in the human motor cortex, a key ALS-relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, the brain regional vulnerability of ALS-associated genes and the genetic link between region-specific genes and ALS risk remain largely unclear. Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics. We benchmarked SpatialE against another enrichment tool (multimodal intersection analysis) using spatial transcriptomics data from both human and mouse brain tissues. To investigate regional vulnerability, we analysed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function variants detected by whole-genome sequencing in ALS patients and controls, then analysed differential gene expression in the TargetALS RNA-sequencing dataset. SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than multimodal intersection analysis in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogeneous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 of the motor cortex, with abundant expression of upper motor neurons and layer 5 excitatory neurons. Burden analyses of rare loss-of-function variants in Layer 5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6814 ALS patients and 3324 controls (P = 0.029). Gene expression analyses in CNS tissues revealed downregulation of NOMO1 in ALS, which is consistent with a loss-of-function disease mechanism. In conclusion, our integrated spatial transcriptomics and genomic analyses identified regional brain vulnerability in ALS and the association of a layer 5 gene (NOMO1) with ALS risk.

Facilely Modified Nickel-Based Hole Transporting Layers for Organic Solar Cells with 19.12% Efficiency and Enhanced Stability.

Hole transporting layers (HTLs), strategically positioned between electrode and light absorber, play a pivotal role in shaping charge extraction and transport in organic solar cells (OSCs). However, the commonly used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) HTL, with its hygroscopic and acidic nature, undermines the operational durability of OSC devices. Herein, an environmentally friendly approach is developed utilizing nickel acetate tetrahydrate (NiAc·4H2O) and [2-(9H-carbazol-9-yl)ethyl] phosphonic acid (2PACz) as the NiAc·4H2O/2PACz HTL, aiming at overcoming the limitations posed by the conventional PEDOT:PSS one. Encouragingly, a remarkable power conversion efficiency (PCE) of 19.12% is obtained for the OSCs employing NiAc·4H2O/2PACz as the HTL, surpassing that of devices with the PEDOT:PSS HTL (17.59%), which is ranked among the highest ones of OSCs. This improvement is attributed to the appropriate work function, enhanced hole mobility, facilitated exciton dissociation efficiency, and lower recombination loss of NiAc·4H2O/2PACz-based devices. Furthermore, the NiAc·4H2O/2PACz-based OSCs exhibit superior operational stability compared to their PEDOT:PSS-based counterparts. Of significant note, the NiAc·4H2O/2PACz HTL demonstrates a broad generality, boosting the PCE of the PM6:PY-IT and PM6:Y6-based OSCs from 16.47% and 16.79% (with PEDOT:PSS-based analogs as HTLs) to 17.36% and 17.57%, respectively. These findings underscore the substantial potential of the NiAc·4H2O/2PACz HTL in advancing OSCs, offering improved performance and stability, thereby opening avenue for highly efficient and reliable solar energy harvesting technologies.

Decoupling the roles of Ni and Co in anionic redox activity of Li-rich NMC cathodes.

Li[LixNiyMnzCo1-x-y-z]O2 (lithium-rich NMCs) are benchmark cathode materials receiving considerable attention due to the abnormally high capacities resulting from their anionic redox chemistry. Although their anionic redox mechanisms have been much investigated, the roles of cationic redox processes remain underexplored, hindering further performance improvement. Here we decoupled the effects of nickel and cobalt in lithium-rich NMCs via a comprehensive study of two typical compounds, Li1.2Ni0.2Mn0.6O2 and Li1.2Co0.4Mn0.4O2. We discovered that both Ni3+/4+ and Co4+, generated during cationic redox processes, are actually intermediate species for triggering oxygen redox through a ligand-to-metal charge-transfer process. However, cobalt is better than nickel in mediating the kinetics of ligand-to-metal charge transfer by favouring more transition metal migration, leading to less cationic redox but more oxygen redox, more O2 release, poorer cycling performance and more severe voltage decay. Our work highlights a compositional optimization pathway for lithium-rich NMCs by deviating from using cobalt to using nickel, providing valuable guidelines for future high-capacity cathode design.

Remote Charging and Degradation Suppression for the Quantum Battery.

The quantum battery (QB) makes use of quantum effects to store and supply energy, which may outperform its classical counterpart. However, there are two challenges in this field. One is that the environment-induced decoherence causes the energy loss and aging of the QB, the other is that the decreasing of the charger-QB coupling strength with increasing their distance makes the charging of the QB become inefficient. Here, we propose a QB scheme to realize a remote charging via coupling the QB and the charger to a rectangular hollow metal waveguide. It is found that an ideal charging is realized as long as two bound states are formed in the energy spectrum of the total system consisting of the QB, the charger, and the electromagnetic environment in the waveguide. Using the constructive role of the decoherence, our QB is immune to the aging. Additionally, without resorting to the direct charger-QB interaction, our scheme works in a way of long-range and wireless-like charging. Effectively overcoming the two challenges, our result supplies an insightful guideline to the practical realization of the QB by reservoir engineering.

High-performance n-type organic thermoelectrics enabled by modulating cyano-functionalized polythiophene backbones.

The scarcity of n-type polymers with high electrical conductivity (σ) and power factor (PF) is the major challenge for organic thermoelectrics (OTEs). By integrating cyano functionalities and an intramolecular conformation lock, we herein synthesize a new electron-deficient building block, CNg4T2, bearing long 1,4,7,10-tetraoxahendecyl side chains, and then further develop two n-type polythiophene derivatives, CNg4T2-2FT and CNg4T2-CNT2, with 3,4-difluorothiophene and 3,3'-dicyano-2,2'-bithiophene as co-units, respectively. Compared with CNg4T2-2FT, CNg4T2-CNT2 features a deeper-positioned lowest unoccupied molecular orbital (LUMO) while maintaining a high degree of backbone coplanarity. As a consequence, the CNg4T2-CNT2 film with molecular dopant N-DMBI delivered an impressive σ of 13.2 S cm-1 and a high PF of up to 10.84 µW m-1 K-2, significantly outperforming CNg4T2-2FT and benchmark n-type polymer N2200 films. To the best of our knowledge, this PF of CNg4T2-CNT2 devices is the highest value for n-type polythiophenes in OTEs. Further characterizations indicate that the high performance of CNg4T2-CNT2-based devices is attributed to the high doping efficiency and ordered packing of polymer chains. Our study demonstrates that CNg4T2 is a highly appealing electron-deficient building block for n-type OTE polymers and also suggests that fine-tuning of the polymer backbone is a powerful approach to accessing high-performance n-type polymers for OTE devices.

Valence-band hybridization in sulphides.

The hybridization state in solids often defines the critical chemical and physical properties of a compound. However, it is difficult to spectroscopically detect and evaluate hybridization beyond just general fingerprint signatures. Here, the valence-band hybridization of metal d-derived bands (short: "metal d bands") in selected metal sulphides is studied with a combined spectroscopic and theoretical approach to derive deeper insights into the fundamental nature of such compounds. The valence bands of the studied sulphides are comprised of hybrid bands derived from the metal d, S 3s, and S 3p states. Employing S K and L2,3 X-ray emission spectroscopy and spectra calculations based on density functional theory, the degree of hybridization (i.e., the covalency) of these bands can be directly probed as a function of their relative energies. We find that the relative intensity of the "metal d band" features in the spectra scales with the inverse square of the energy separation to the respective sulfur-derived bands, which can be analytically derived from a simple two-orbital model. This study demonstrates that soft X-ray emission spectroscopy is a powerful tool to study valence state hybridization, in particular in combination with hard X-ray emission spectroscopy, promising a broad impact in many research fields.

Effect of adductor canal block combined with infiltration between the popliteal artery and posterior capsular of the knee on chronic pain after total knee arthroplasty: a prospective, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Total knee arthroplasty (TKA) is accompanied by severe postoperative pain, which is reported to be an important cause of chronic pain. Ultrasound-guided adductor canal block (ACB) combined with infiltration between the popliteal artery and posterior capsular of the knee (IPACK) has been proven to have a better effect on relieving acute pain after TKA. However, whether it has a significant effect on the incidence of chronic pain after TKA has not been reported. This trial was designed to investigate the effect of ultrasound-guided ACB combined with IPACK on the incidence and intensity of chronic pain after TKA. METHODS: In this prospective, randomized, double-blind, placebo-controlled study, 100 subjects scheduled for TKA were randomly (1:1) divided into two groups: the ropivacaine group and the placebo group. Patients in each group received ultrasound-guided ACB + IPACK procedures with 0.25% ropivacaine or equal volume normal saline. All patients received multimodal analgesia. Pain intensity was assessed using the Numerical Rating Scale (NRS). The primary outcome was the incidence of chronic pain at 3 months after TKA by telephone follow-up. In addition, pain intensity in early resting and mobilized states, chronic pain intensity, the time to first rescue analgesia; opioid consumption; CRP and IL-6 after the operation; length of postoperative hospital stay; and cost of hospitalization and postoperative complications; as well as the function of the knee in the early stage after the operation, were recorded. RESULTS: Ninety-one participants were included in the final analysis. At 3 months, the incidence of chronic pain was 30.4% in the ropivacaine group, significantly lower than 51.1% in the placebo group. Compared with the placebo group, the ACB + IPACK with ropivacaine group had significantly lower pain scores at 4 hours, 8 hours, 16 hours, and 24 hours after the operation; increased the knee range of motion at 8 hours and 24 hours after the operation; and a significantly decreased incidence of chronic pain at 3 months after the operation. During the follow-up period, there were no nerve block-related complications in either group. CONCLUSION: In the context of multimodal analgesia protocols, ACB combined with IPACK before surgery decreases the incidence and intensity of chronic pain 3 months after TKA compared with placebo injection. In addition, it reduces the NRS scores, whether at rest or during mobilization, and improves knee function within 24 hours after TKA. TRIAL REGISTRATION: This trial was registered in the China Clinical Trial Center (registration number ChiCTR2200065300) on November 1, 2022.

Effect of deep neuromuscular block on the quality of early recovery after sleeve gastrectomy in obese patients: a randomized controlled trial.

BACKGROUND: Deep neuromuscular block (NMB) has been shown to improve surgical conditions and alleviate post-operative pain in bariatric surgery compared with moderate NMB. We hypothesized that deep NMB could also improve the quality of early recovery after laparoscopic sleeve gastrectomy (LSG). METHODS: Eighty patients were randomized to receive either deep (post-tetanic count 1-3) or moderate (train-of-four count 1-3) NMB. The QoR-15 questionnaire was used to evaluate the quality of early recovery at 1 day before surgery (T0), 24 and 48 h after surgery (T2, T3). Additionally, we recorded diaphragm excursion (DE), postoperative pain, surgical condition, cumulative dose of analgesics, time of first flatus and ambulation, post-operative nausea and vomiting, time of tracheal tube removal and hospitalization time. MAIN RESULTS: The quality of recovery was significantly better 24 h after surgery in patients who received a deep versus moderate block (114.4 ± 12.9 versus 102.1 ± 18.1). Diaphragm excursion was significantly greater in the deep NMB group when patients performed maximal inspiration at T2 and T3 (P < 0.05). Patients who underwent deep NMB reported lower visceral pain scores 40 min after surgery; additionally, these patients experienced lower pain during movement at T3 (P < 0.05). Optimal surgical conditions were rated in 87.5% and 64.6% of all measurements during deep and moderate NMB respectively (P < 0.001). The time to tracheal tube removal was significantly longer in the deep NMB group (P = 0.001). There were no differences in other outcomes. CONCLUSION: In obese patients receiving deep NMB during LSG, we observed improved QoR-15 scores, greater diaphragmatic excursions, improved surgical conditions, and visceral pain scores were lower. More evidence is needed to determine the effects of deep NMB on these outcomes. TRIAL REGISTRATION: ChiCTR2200065919. Date of retrospectively registered: 18/11/2022.

Functionalized Phenanthrene Imide-Based Polymers for n-Type Organic Thin-Film Transistors.

High-performing n-type polymers are crucial for the advance of organic electronics field, however strong electron-deficient building blocks with optimized physicochemical properties for constructing them are still limited. The imide-functionalized polycyclic aromatic hydrocarbons (PAHs) with extended π-conjugated framework, high electron deficiency and good solubility serve as promising candidates for developing high-performance n-type polymers. Among the PAHs, phenanthrene (PhA) features a well-delocalized aromatic π-system with multiple modifiable active sites . However, the PhA-based imides are seldom studied, mainly attributed to the synthetic challenge. Herein, we report two functionalized PhAs, CPOI and CPCNI, by simultaneously incorporating imide with carbonyl or dicyanomethylene onto PhA. Notably, the dicyanomethylene-modified CPCNI exhibits a well stabilized LUMO energy level (-3.84 eV), attributed to the synergetic inductive effect from imide and cyano groups. Subsequently, based on CPOI and CPCNI, two polymers PCPOI-Tz and PCPCNI-Tz were developed. Applied to organic thin-film transistors, owing to the strong electron-deficiency of CPCNI, polymer PCPCNI-Tz shows an improved electron mobility and largely decreased threshold voltage compared with PCPOI-Tz. This work affords two structurally novel electron-deficient building blocks and highlights the effectiveness of dual functionalization of PhAs with strong electron-withdrawing groups for devising n-type polymers.

Cyano-Functionalized Pyrazine: A Structurally Simple and Easily Accessible Electron-Deficient Building Block for n-Type Organic Thermoelectric Polymers.

Developing low-cost and high-performance n-type polymer semiconductors is essential to accelerate the application of organic thermoelectrics (OTEs). To achieve this objective, it is critical to design strong electron-deficient building blocks with simple structure and easy synthesis, which are essential for the development of n-type polymer semiconductors. Herein, we synthesized two cyano-functionalized highly electron-deficient building blocks, namely 3,6-dibromopyrazine-2-carbonitrile (CNPz) and 3,6-Dibromopyrazine-2,5-dicarbonitrile (DCNPz), which feature simple structures and facile synthesis. CNPz and DCNPz can be obtained via only one-step reaction and three-step reactions from cheap raw materials, respectively. Based on CNPz and DCNPz, two acceptor-acceptor (A-A) polymers, P(DPP-CNPz) and P(DPP-DCNPz) are successfully developed, featuring deep-positioned lowest unoccupied molecular orbital (LUMO) energy levels, which are beneficial to n-type organic thin-film transistors (OTFTs) and OTEs performance. An optimal unipolar electron mobility of 0.85 and 1.85 cm2 V-1 s-1 is obtained for P(DPP-CNPz) and P(DPP-DCNPz), respectively. When doped with N-DMBI, P(DPP-CNPz) and P(DPP-DCNPz) show high n-type electrical conductivities/power factors of 25.3 S cm-1 /41.4 µW m-1 K-2 , and 33.9 S cm-1 /30.4 µW m-1 K-2 , respectively. Hence, the cyano-functionalized pyrazine CNPz and DCNPz represent a new class of structurally simple, low-cost and readily accessible electron-deficient building block for constructing n-type polymer semiconductors.

Integrated transcriptome and proteome revealed that the declined expression of cell cycle-related genes associated with follicular atresia in geese.

BACKGROUND: Geese exhibit relatively low reproductive performance, and follicular atresia is an important factor that restricts the egg production of geese. Systematic analysis of the regulation of follicle atresia in geese through transcriptome and proteome levels could provide meaningful information on clarifying the mechanism of follicle atresia in poultry. RESULT: The granulosa cell layer was loose, disintegrated and showed apoptosis in atretic follicles and remained intact in normal follicles. The hormone levels of FSH and LH were significantly decreased in the atresia follicles compared to the normal follicles (P < 0.05). A total of 954 differentially expressed genes (DEGs, 315 increased and 639 decreased) and 161 differentially expressed proteins (DEPs, 61 increased and 100 decreased) were obtained in atresia follicles compared to normal follicles, of which, 15 genes were differentially expressed in both transcriptome and proteome. The DEGs were mainly enriched in sodium transmembrane transport, plasma membrane, and transmembrane transporter activity based on the GO enrichment analysis and in the cell cycle pathway based on the KEGG enrichment analysis. The DEPs were mainly enriched in localization, lysosome, and phospholipid-binding based on the GO enrichment analysis. Candidate genes Smad2/3, Smad4, Annexin A1 (ANXA1), Stromelysin-1 (MMP3), Serine/threonine-protein kinase (CHK1), DNA replication licensing factor (MCM3), Cyclin-A2 (CCNA2), mitotic spindle assembly checkpoint protein (MAD2), Cyclin-dependent kinase 1 (CDK1), fibroblast growth factor 12 (FGF12), and G1/S-specific cyclin-D1 (CCND1) were possibly responsible for the regulation of atresia. CONCLUSION: The cell cycle is an important pathway for the regulation of follicular atresia. Sodium outflow and high expression of MMP3 and MMP9 could be responsible for structural destruction and apoptosis of follicular cells.

Log odds of positive lymph nodes as a novel prognostic predictor for gastric cancer: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to summarize the predictive and prognostic ability of the log odds of positive lymph nodes (LODDS) staging system and compare it with pathological N (pN) classification and the ratio-based lymph node system (rN) for the overall survival (OS) of gastric cancer (GC). METHODS: Through a systematic review till March 7, 2022, we identified population-based studies that reported the prognostic effects of LODDS in patients with GC. We compare the predictive effectiveness of the LODDS staging system with that of the rN and pN classification systems for the OS of GC. RESULTS: Twelve studies comprising 20,312 patients were included in this systematic review and meta-analysis. The results showed that LODDS1, LODDS2, LODDS3, and LODDS4 in GC patients were correlated with poor OS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.62, 95% CI (1.42, 1.85); LODDS2 vs. LODDS0: HR = 2.47, 95% CI (2.02, 3.03); LODDS3 vs. LODDS0: HR = 3.15, 95% CI (2.50, 3.97); LODDS4 vs. LODDS0: HR = 4.55, 95% CI (3.29, 6.29)). Additionally, significant differences in survival were observed among patients with different LODDS classifications (all P-values were < 0.001) with the same rN and pN classifications. Meanwhile, for patients with different pN or rN classifications with the same LODDS classification, prognosis was highly similar. CONCLUSION: The findings show that LODDS is correlated with the prognosis of GC patients and is superior to the pN and rN classifications for prognostic assessment.

Reversible Entropy-Driven Defect Migration and Insulator-Metal Transition Suppression in VO2 Nanostructures for Phase-Change Electronic Switching.

Oxygen defects are among essential issues and required to be manipulated in correlated electronic oxides with insulator-metal transition (IMT). Besides, surface and interface control are necessary but challenging in field-induced electronic switching towards advanced IMT-triggered transistors and optical modulators. Herein, we demonstrated reversible entropy-driven oxygen defect migrations and reversible IMT suppression in vanadium dioxide (VO2 ) phase-change electronic switching. The initial IMT was suppressed with oxygen defects, which is caused by the entropy change during reversed surface oxygen ionosorption on the VO2 nanostructures. This IMT suppression is reversible and reverts when the adsorbed oxygen extracts electrons from the surface and heals defects again. The reversible IMT suppression observed in the VO2 nanobeam with M2 phase is accompanied by large variations in the IMT temperature. We also achieved irreversible and stable IMT by exploiting an Al2 O3 partition layer prepared by atomic layer deposition (ALD) to disrupt the entropy-driven defect migration. We expected that such reversible modulations would be helpful for understanding the origin of surface-driven IMT in correlated vanadium oxides, and constructing functional phase-change electronic and optical devices.

Electric-field control of tri-state phase transformation with a selective dual-ion switch.

Materials can be transformed from one crystalline phase to another by using an electric field to control ion transfer, in a process that can be harnessed in applications such as batteries, smart windows and fuel cells. Increasing the number of transferrable ion species and of accessible crystalline phases could in principle greatly enrich material functionality. However, studies have so far focused mainly on the evolution and control of single ionic species (for example, oxygen, hydrogen or lithium ions). Here we describe the reversible and non-volatile electric-field control of dual-ion (oxygen and hydrogen) phase transformations, with associated electrochromic and magnetoelectric effects. We show that controlling the insertion and extraction of oxygen and hydrogen ions independently of each other can direct reversible phase transformations among three different material phases: the perovskite SrCoO3-δ (ref. 12), the brownmillerite SrCoO2.5 (ref. 13), and a hitherto-unexplored phase, HSrCoO2.5. By analysing the distinct optical absorption properties of these phases, we demonstrate selective manipulation of spectral transparency in the visible-light and infrared regions, revealing a dual-band electrochromic effect that could see application in smart windows. Moreover, the starkly different magnetic and electric properties of the three phases-HSrCoO2.5 is a weakly ferromagnetic insulator, SrCoO3-δ is a ferromagnetic metal, and SrCoO2.5 is an antiferromagnetic insulator-enable an unusual form of magnetoelectric coupling, allowing electric-field control of three different magnetic ground states. These findings open up opportunities for the electric-field control of multistate phase transformations with rich functionalities.

Investigation of a Fused in Sarcoma Splicing Mutation in a Chinese Amyotrophic Lateral Sclerosis Patient.

OBJECTIVE: Genetic mutations of fused in sarcoma (FUS) causing amyotrophic lateral sclerosis (ALS) may disrupt mRNA splicing events. For example, the FUS c.1394-2delA variant was reported in two western ALS patients, but its molecular mechanism is unclear. In this study, we aim to investigate FUS splice site mutations in Chinese ALS patients. METHODS: Sanger sequencing was used to identify FUS splicing mutations in Chinese ALS patients. We combined a deep learning tool (SpliceAI), RNA sequencing, and RT-PCR/RT-qPCR to analyze the effect of FUS c.1394-2delA mutation on RNA splicing and expression. AlphaFold was used to predict the protein structure of mutant FUS. In transfected cell lines, we used immunofluorescence to assess cytoplasmic mislocalization of mutant FUS protein. RESULTS: We identified a de novo FUS splice acceptor site mutation (c.1394-2delA, p. Gly466Valfs*14) in one Chinese sporadic ALS patient, which is linked to exon 14 skipping, and upregulated total FUS mRNA expression. The FUS splice site mutation was predicted to be translated into a truncated protein product at C-terminal. In vitro studies revealed that the FUS mutation increased cytoplasmic mislocalization in both HEK293T and SH-SY5Y cells. CONCLUSIONS: We identified a de novo FUS splicing mutation (c.1394-2delA, p. Gly466Valfs*14) in 1 out of 233 Chinese ALS patients. It caused abnormal RNA splicing, upregulated gene expression, truncated FUS translation, and cytosolic mislocalization. Our findings suggested that FUS splice site mutation is rare in Chinese ALS patients and extended our knowledge of molecular mechanisms of the FUS c.1394-2delA mutation.

Burden of gastroesophageal reflux disease in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of disease study 2019.

INTRODUCTION: For effective preventive strategies against GORD (gastro-esophageal reflux disease), we assessed the GORD burden from 1990 to 2019. METHODS: The burden of GORD between 1990 and 2019 was evaluated globally, regionally, and nationally. Using ASIR (age-standardized incidence), ASYLDs (age-standardized years lived with disabilitys), we compared them to the GBD world population per 100,000. The estimates were based on 95% uncertainty intervals (UIs). The AAPC (average annual percent change) in incidence, YLDs, along with prevalence rates with associated 95% CIs were estimated. RESULTS: Data to estimate the burden of GORD are scarce till now. The global ASIR of GORD in 2019 was 3792.79 per 100,000, an increase AAPC of 0.112% from 1990. The prevalence of GORD increased with a AAPC of 0.096% to 9574.45 per 100,000. Global ASYLDs in 2019 was 73.63, an increase AAPC of 0.105% from 1990. The GORD burden varies greatly depending on the development level and geographical location. USA demonstrated the most obvious decreasing trend in burden of GORD, while Sweden had an increasing trend. That the increase in GORD YLDs was mediated primarily by the growth and aging of population, was revealed by decomposition analyses. There was an inverse relationship between SDI (socio-demographic index) and GORD-burden. Frontier analyses revealed significant scope of improvement in the status of development at all levels. CONCLUSION: GORD is a public health challenge, especially in Latin America. Some SDI quintiles had declining rates, while some countries experienced increased rates. Thus, resources should be allocated for preventative measures based on country-specific estimates.

Development and validation of an RBP gene signature for prognosis prediction in colorectal cancer based on WGCNA.

BACKGROUND: RNA binding proteins (RBPs) have been implicated in oncogenesis and progression in various cancers. However, the potential value of RBPs as prognostic indicators and therapeutic targets in colorectal cancer (CRC) requires further investigation. METHODS: Four thousand eighty two RBPs were collected from literature. The weighted gene co-expression network analysis (WGCNA) was performed to identify prognosis-related RBP gene modules based on the data attained from the TCGA cohorts. LASSO algorithm was conducted to establish a prognostic risk model, and the validity of the proposed model was confirmed by an independent GEO dataset. Functional enrichment analysis was performed to reveal the potential biological functions and pathways of the signature and to estimate tumor immune infiltration. Potential therapeutic compounds were inferred utilizing CMap database. Expressions of hub genes were further verified through the Human Protein Atlas (HPA) database and RT-qPCR. RESULTS: One thousand seven hundred thirty four RBPs were differently expressed in CRC samples and 4 gene modules remarkably linked to the prognosis were identified, based on which a 12-gene signature was established for prognosis prediction. Multivariate Cox analysis suggested this signature was an independent predicting factor of overall survival (P < 0.001; HR:3.682; CI:2.377-5.705) and ROC curves indicated it has an effective predictive performance (1-year AUC: 0.653; 3-year AUC:0.673; 5-year AUC: 0.777). GSEA indicated that high risk score was correlated with several cancer-related pathways, including cytokine-cytokine receptor cross talk, ECM receptor cross talk, HEDGEHOG signaling cascade and JAK/STAT signaling cascade. ssGSEA analysis exhibited a significant correlation between immune status and the risk signature. Noscapine and clofazimine were screened as potential drugs for CRC patients with high-risk scores. TDRD5 and GPC1 were identified as hub genes and their expression were validated in 15 pairs of surgically resected CRC tissues. CONCLUSION: Our research provides a depth insight of RBPs' role in CRC and the proposed signature are helpful to the personalized treatment and prognostic judgement.

Identification of the Shared Gene Signatures and Biological Mechanisms in Hyperplastic Enlarged Lobular Units and Breast Cancer.

Breast cancer is a common cancer worldwide. Hyperplastic enlarged lobular units (HELUs) are common changes in the breasts of adult women. HELUs may be closely related to the occurrence and development of breast cancer. In this study, genes that are commonly contained in the expression profiles of the genomes of the two diseases and have significant differences in expression before and after the respective diseases were identified. Various enrichment analyses were performed according to the expression levels of these differentially expressed genes. Furthermore, LASSO regression analysis was performed on the differentially expressed genes to identify genes significantly related to survival. The optimal risk model for the survival of patients with breast cancer was established, and the accuracy of the model was verified on multiple data sets. A gene combination containing 17 genes was ultimately determined to be an independent prognostic factor. Kaplan‒Meier survival analysis demonstrated the good performance of this risk model. The study found that Shared Gene Signatures and Biological Mechanisms in Hyperplastic Enlarged Lobular Units and Breast Cancer, screened 17 important Shared Gene Signatures of Hyperplastic Enlarged Lobular Units which are closely related to the survival of breast cancer patients through machine learning, and established a prognosis model with high-accuracy, which is worthy of further exploration.

Geometrical Bounds on Irreversibility in Squeezed Thermal Bath.

Irreversible entropy production (IEP) plays an important role in quantum thermodynamic processes. Here, we investigate the geometrical bounds of IEP in nonequilibrium thermodynamics by exemplifying a system coupled to a squeezed thermal bath subject to dissipation and dephasing, respectively. We find that the geometrical bounds of the IEP always shift in a contrary way under dissipation and dephasing, where the lower and upper bounds turning to be tighter occur in the situation of dephasing and dissipation, respectively. However, either under dissipation or under dephasing, we may reduce both the critical time of the IEP itself and the critical time of the bounds for reaching an equilibrium by harvesting the benefits of squeezing effects in which the values of the IEP, quantifying the degree of thermodynamic irreversibility, also become smaller. Therefore, due to the nonequilibrium nature of the squeezed thermal bath, the system-bath interaction energy has a prominent impact on the IEP, leading to tightness of its bounds. Our results are not contradictory with the second law of thermodynamics by involving squeezing of the bath as an available resource, which can improve the performance of quantum thermodynamic devices.

Source of Rate Acceleration for Carbocation Cyclization in Biomimetic Supramolecular Cages.

The results of quantum chemical and molecular dynamics calculations reveal that polyanionic gallium-based cages accelerate cyclization reactions of pentadienyl alcohols as a result of substrate cage interactions, preferential binding of reactive conformations of substrate/H3O+ pairs, and increased substrate basicity. However, the increase in basicity dominates. Experimental structure-activity relationship studies in which the metal vertices and overall charge of the cage are varied confirm the model derived via calculations.