Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Propionic acid ameliorates cognitive function through immunomodulatory effects on Th17 cells in perioperative neurocognitive disorders.

Background: Elderly patients undergoing surgery are prone to cognitive decline known as perioperative neurocognitive disorders (PND). Several studies have shown that the microglial activation and the decrease of short-chain fatty acids (SCFAs) in gut induced by surgery may be related to the pathogenesis of PND. The purpose of this study was to determine whether microglia and short-chain fatty acids were involved in cognitive dysfunction in aged rats. Methods: Male wild-type Wistar rats aged 11-12 months were randomly divided into control group (Ctrl: Veh group), propionic acid group (Ctrl: PA group), exploratory laparotomy group (LP: Veh group) and propionic acid + exploratory laparotomy group (LP: PA group) according to whether exploratory laparotomy (LP) or PA pretreatment for 21 days was performed. The motor ability of the rats was evaluated by open field test on postoperative day 3 (POD3), and then the cognitive function was evaluated by Y-maze test and fear conditioning test. The expression of IL-1ß, IL-6, RORγt and IL-17A mRNA in hippocampus was detected by RT-qPCR, the expression of IL-17A and IL-17RA in hippocampus was detected by Western blot, and the activation of microglia was detected by immunofluorescence. Results: The PND rat model was successfully established by laparotomy. Compared with Ctrl: Veh group, the body weight of LP: Veh group decreased, the percentage of spontaneous alternations in Y maze decreased (P < 0.001), and the percentage of freezing time in contextual fear test decreased (P < 0.001). Surgery triggers neuroinflammation, manifested as the elevated levels of the inflammatory cytokines IL-1ß (P < 0.001) and IL-6 (P < 0.001), the increased expression of the transcription factor RORγt (P = 0.0181, POD1; P = 0.0073, POD5)and major inflammatory cytokines IL-17A (P = 0.0215, POD1; P = 0.0071, POD5), and the increased average fluorescence intensity of Iba1 (P < 0.001, POD1; P < 0.001, POD5). After PA preconditioning, the recovery of rats in LP: PA group was faster than that in LP: Veh group as the body weight lost on POD1 (P = 0.0148) was close to the baseline level on POD5 (P = 0.1846), and they performed better in behavioral tests. The levels of IL-1ß (P < 0.001) and IL-6 (P = 0.0035) inflammatory factors in hippocampus decreased on POD1 and the average fluorescence intensity of Iba1 decreased (P = 0.0024, POD1; P < 0.001, POD5), representing the neuroinflammation was significantly improved. Besides, the levels of RORγt mRNA (P = 0.0231, POD1; P = 0.0251, POD5) and IL-17A mRNA (P = 0.0208, POD1; P = 0.0071, POD5) in hippocampus as well as the expression of IL-17A (P = 0.0057, POD1; P < 0.001, POD5) and IL-17RA (P = 0.0388) decreased. Conclusion: PA pretreatment results in reduced postoperative neuroinflammation and improved cognitive function, potentially attributed to the regulatory effects of PA on Th17-mediated immune responses.

Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight.

The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing. Carbohydrates were the major source of total energy (56.61%), followed by fat (27.92%) and protein (15.46%). The rate of infant LBW was 7.8%, which was positively correlated with maternal carbohydrate intake. In the pregnancy gut microbiota, Bacteroides ovatus and Dorea spp. were indirectly and directly negatively associated with fetal growth, respectively; Rosenburia faecis was directly positively associated with neonatal birth weight. Maternal hypertension during pregnancy altered the microbiota features and was associated with poor fetal growth. Microbiota-accessible carbohydrates can modify the composition and function of the pregnancy gut microbiota, thus providing a potential marker to modulate deviations from dietary patterns, particularly in women at risk of hypertension during pregnancy, to prevent neonatal LBW.

In-Depth Insight into Corrosion Inhibition Performance of Sweet Potato Leaf Extract as a Green and Efficient Inhibitor for 6N01 Al Alloy in the Seawater: Experimental and Theoretical Perspectives.

Corrosion protection of metal has become an important and urgent topic, which requires the development of an inexpensive, environmentally friendly, and highly efficient corrosion inhibitor. Herein, a sweet potato leaf extract (SPL) was obtained by a simple water-based extraction method and then as a green corrosion inhibitor for 6N01 Al alloy in the seawater was well investigated by the weight loss method and various electrochemical tests. Fourier transform infrared (FT-IR) and ultraviolet-visible (UV-vis) spectroscopies were carried out to investigate the compositions of SPL. The findings from the potentiodynamic polarization (PDP) curves suggest that SPL functions as a typical mixed-type corrosion inhibitor. Notably, the maximum corrosion inhibition efficiency reaches 94.6% following a 36 h immersion period at 25 °C. The adsorption behavior of SPL on the Al alloy surface belongs to the Langmuir adsorption isotherm. The Gibbs free energy value illustrates that the adsorption of SPL contains both physisorption and chemisorption. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) indicate that SPL is firmly attached to the Al alloy surface by making a protective layer, which can effectively inhibit the corrosion of the Al alloy in the seawater. Furthermore, quantum chemical calculations were applied to validate the chemical adsorption and elucidate the relationship between the electronic structure of the active components in SPL and their effectiveness in corrosion inhibition.

Triglyceride-Glucose Index is an Independent Risk Factor for Hepatocellular Carcinoma Development in Patients with HBV-Related Liver Cirrhosis.

Aim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC. Results: The median follow-up time was 37 months (range: 6-123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P<0.01), DC (P<0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P<0.01), and HBV DNA positivity (P<0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, <0.01, 0.05, and <0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P<0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively. Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

[Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with GATA2 Gene Mutation].

OBJECTIVE: To investigate the clinical characteristics, coexisting gene mutations and prognosis of acute myeloid leukemia (AML) patients with GATA2 gene mutation. METHODS: The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively, the next-generation sequencing technology was used to detect the mutated genes in those patients. The clinical characteristics of AML patients with GATA2 mutations, the co-mutated genes of GATA2 mutations, and the effect of GATA2 mutation on prognosis were analyzed. RESULTS: A total of 23 patients (6.2%) with GATA2 mutation was detected in 370 AML patients. Compared with GATA2 non-mutation group, patients in GATA2 mutation group were mostly normal karyotypes (P =0.037) and in low-risk cytogenetic stratification (P =0.028). The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group (P =0.010, P =0.009). There were no statistically significant differences between the two groups in terms of sex, age, white blood cell count (WBC), platelet count, hemoglobin, bone marrow (BM) blast, induction chemotherapy regimen and CR rate (P >0.05). Among the 23 patients with GATA2 mutation, the most common co-mutated genes were CEBPAdm, NRAS (both 39.1%), NPM1, FLT3, TET2, WT1 (all 17.4%), ASXL1 and IDH1 (both 13.0%). Survival analysis showed that there was no statistical difference in 5-year overall survival (OS) and leukemia-free survival (LFS) rates between patients with and without GATA2 mutations in whole cohort (n=370) (P =0.306, P =0.308). Among 306 patients without CEBPAdm, the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group, but the difference was not statistically significant (P =0.092, P =0.056). Among 64 patients with CEBPAdm, there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group (P =0.104), but the 5-year LFS rate of the GATA2 mutation group was significantly decreased (P =0.047). Among the 23 patients with GATA2 mutation, 16 cases received the "3+7" induction regimen, of which 12 cases received allogeneic hematopoietic stem cell transplantation (allo-HSCT); 7 cases received the "DCAG" induction regimen, of which 3 cases received allo-HSCT. The CR rate was not statistically different between the "3+7" regimen group and the "DCAG" regimen group (P =1.000). The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group (P =0.021, P =0.020). CONCLUSION: GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations. The prognostic significance of GATA2 is influenced by CEBPAdm. The choice of "3+7" or "DCAG" induction regimen in patients with GATA2 mutation does not affect their CR rate, while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

A photoelectrochemical biosensor based on self-calibration platform of carbon-rich plasmonic probe with near-infrared driving signal amplification.

Exploring the photochemical (PEC) method induced by low-energy light source makes great significance to achieve high stability and accurate analysis. A sensing platform driven by near-infrared (NIR) light was designed by making the biochemically encoded carbon rich plasmonic hybrid (CPH) probe, the peptide@C-Mo2C. The inherent plasmonic effect of C-Mo2C CPH can directly absorb NIR light, thus starting effective electronic-hole pairs separation. Moreover, the photothermal effect of C-Mo2C CPH also promoted the reaction yield of photothermal catalyst reaction on sensing interface to assist the PEC signal amplification. In the presence of target trypsin, it cleaves the peptides, resulting in the release of peptide@C-Mo2C probe from interface, which leads to a relative decrease in PEC signal. More importantly, a self-calibration system consisting of two independent PEC test channels attempted to eliminate the influence of background signal and baseline drift. The test channel was used to specify the recognition target, while the blank channel was used as a reference. Therefore, the signal difference between two channels was recorded, so as to obtain results with less error and higher stability. In this NIR driven PEC sensor, the carbon rich probe with direct and efficient NIR light conversion promoted the sensitivity and a self-calibration system guaranteed the stability which provided innovative thoughts for developing ingenious PEC sensor.

Flow Channel with Wrinkles and Calcium Sites in a Ca-MOF for Direct One-Step Ethylene Purification from C2 Gases and MTO Products Separation.

The strategy of flow channel with wrinkles and calcium sites for single-step C2H4 purification from C2 gases and methanol-to-olefins (MTO) products separation was realized in FJI-Y9. The adsorption amounts showed a total reversal order of C3H6 > C2H6 > C2H2 > C2H4 at 298 K. Modeling indicated that the wrinkles and Ca2+ facilitated the full contact of C3H6 and C2H6. Breakthrough experiments illustrated that FJI-Y9 could yield pure C2H4 in a single step with a productivity of 0.78 mmol g-1. In a lone adsorption/desorption cycle for MTO product separation, the productivities of C3H6 and C2H4 were 1.96 and 1.29 mol g-1, standing as the highest recorded values.

Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses.

Background: Growing evidence suggests that headache disorders and atopic dermatitis share similar pathological mechanisms and risk factors. The aim of this study was to assess the risk for headache disorders in patients with atopic dermatitis. Methods: We systematically searched the PubMed and Embase databases from inception to December 1, 2023, for observational studies that examined risk of migraine in subjects with atopic dermatitis. Risk estimates from individual studies were pooled using random-effects models. Results: Ten studies with 12,717,747 subjects were included in the meta-analysis. Our results showed that patients with atopic dermatitis were associated with a higher risk of headache disorder (OR, 1.46, 95% CI = 1.36-1.56; P < 0.001; I2 = 98%) or migraine (OR, 1.32, 95% CI = 1.18-1.47; P < 0.001; I2 = 98.9%). Most of the results of the subgroup analyses were consistent with the overall results. Conclusion: The findings of this meta-analysis suggest that atopic dermatitis is a potential risk indicator for headache disorder or migraine. Further studies are still needed to verify our findings due to the substantial heterogeneity in our analyses.

Electrical stress and acid orange 7 synergistically clear the blockage of electron flow in the methanogenesis of low-strength wastewater.

Energy recovery from low-strength wastewater through anaerobic methanogenesis is constrained by limited substrate availability. The development of efficient methanogenic communities is critical but challenging. Here we develop a strategy to acclimate methanogenic communities using conductive carrier (CC), electrical stress (ES), and Acid Orange 7 (AO7) in a modified biofilter. The synergistic integration of CC, ES, and AO7 precipitated a remarkable 72-fold surge in methane production rate compared to the baseline. This increase was attributed to an altered methanogenic community function, independent of the continuous presence of AO7 and ES. AO7 acted as an external electron acceptor, accelerating acetogenesis from fermentation intermediates, restructuring the bacterial community, and enriching electroactive bacteria (EAB). Meanwhile, CC and ES orchestrated the assembly of the archaeal community and promoted electrotrophic methanogens, enhancing acetotrophic methanogenesis electron flow via a mechanism distinct from direct electrochemical interactions. The collective application of CC, ES, and AO7 effectively mitigated electron flow impediments in low-strength wastewater methanogenesis, achieving an additional 34% electron recovery from the substrate. This study proposes a new method of amending anaerobic digestion systems with conductive materials to advance wastewater treatment, sustainability, and energy self-sufficiency.

Human immunodeficiency virus-associated dementia complex with positive 14-3-3 protein in cerebrospinal fluid: A case report.

BACKGROUND: Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical form of dementia characterized by memory deficits and psychomotor slowing. However, HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease (CJD), particularly in patients with acquired immune deficiency syndrome (AIDS). CASE SUMMARY: We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure. The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins. His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern. Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination. Initially, symptomatic treatment and administration of amantadine were pursued for presumed CJD, but the patient's condition continued to deteriorate. By contrast, the patient's condition improved following anti-HIV therapy. This individual is also the only patient with this prognosis to have survived over 4 years. Thus, the diagnosis was revised to HAD. CONCLUSION: In the diagnostic process of rapidly progressive dementia, it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty. The 14-3-3 protein should not be regarded as the definitive marker for CJD. Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision, especially in AIDS patients with potential CJD. Ultimately, a trial of diagnostic treatment may be considered when additional testing is not feasible.

Zwitterion modified chitosan as a high-performance corrosion inhibitor for mild steel in hydrochloric acid solution.

Herein, a novel chitosan Schiff base (CS-FGA) as a sustainable corrosion inhibitor has been successfully synthesized via a simple amidation reaction by using an imidazolium zwitterion and chitosan (CS). The corrosion inhibition property of CS-FGA for mild steel (MS) in a 1.0 M HCl solution was studied by various electrochemical tests and physical characterization methods. The findings indicate that the maximum inhibition efficiency of CS-FGA as a mixed-type inhibitor for MS in 1.0 M HCl solution with 400 mg L-1 reaches 97.6 %, much much higher than the CS and the recently reported chitosan-based inhibitors. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and water contact angle (WCA) results reveal that the CS-FGA molecules firmly adsorb on the MS surface to form a protective layer. The adsorption of CS-FGA on the MS surface belongs to the Langmuir adsorption isotherm containing both the physisorption and chemisorption. According to the X-ray photoelectron spectroscopy (XPS) and UV-vis spectrum, FeN bonds presented on the MS surface further prove the chemisorption between CS-FGA and Fe to generate the stable protective layer. Additionally, theoretical calculations from quantum chemical calculation (DFT) and molecular simulations (MD) were performed to reveal the inhibition mechanism of CS-FGA.

Breast Cancer Classification from Digital Pathology Images via Connectivity-aware Graph Transformer.

Automated classification of breast cancer subtypes from digital pathology images has been an extremely challenging task due to the complicated spatial patterns of cells in the tissue micro-environment. While newly proposed graph transformers are able to capture more long-range dependencies to enhance accuracy, they largely ignore the topological connectivity between graph nodes, which is nevertheless critical to extract more representative features to address this difficult task. In this paper, we propose a novel connectivity-aware graph transformer (CGT) for phenotyping the topology connectivity of the tissue graph constructed from digital pathology images for breast cancer classification. Our CGT seamlessly integrates connectivity embedding to node feature at every graph transformer layer by using local connectivity aggregation, in order to yield more comprehensive graph representations to distinguish different breast cancer subtypes. In light of the realistic intercellular communication mode, we then encode the spatial distance between two arbitrary nodes as connectivity bias in self-attention calculation, thereby allowing the CGT to distinctively harness the connectivity embedding based on the distance of two nodes. We extensively evaluate the proposed CGT on a large cohort of breast carcinoma digital pathology images stained by Haematoxylin & Eosin. Experimental results demonstrate the effectiveness of our CGT, which outperforms state-of-the-art methods by a large margin. Codes are released on https://github.com/wang-kang-6/CGT.

Improvement of Panax notoginseng saponin accumulation triggered by methyl jasmonate under arbuscular mycorrhizal fungi.

Panax notoginseng is a highly valued perennial medicinal herb plant in Yunnan Province, China, and the taproots are the main medicinal parts that are rich in active substances of P. notoginseng saponins. The main purpose of this study is to uncover the physiological and molecular mechanism of Panax notoginseng saponin accumulation triggered by methyl jasmonate (MeJA) under arbuscular mycorrhizal fungi (AMF) by determining physiological indices, high-throughput sequencing and correlation analysis. Physiological results showed that the biomass and saponin contents of P. notoginseng, the concentrations of jasmonic acids (JAs) and the key enzyme activities involved in notoginsenoside biosynthesis significantly increased under AMF or MeJA, but the interactive treatment of AMF and MeJA weakened the effect of AMF, suggesting that a high concentration of endogenous JA have inhibitory effect. Transcriptome sequencing results indicated that differential expressed genes (DEGs) involved in notoginsenoside and JA biosynthesis were significantly enriched in response to AMF induction, e.g., upregulated genes of diphosphocytidyl-2-C-methyl-d-erythritol kinases (ISPEs), cytochrome P450 monooxygenases (CYP450s)_and glycosyltransferases (GTs), while treatments AMF-MeJA and salicylhydroxamic acid (SHAM) decreased the abundance of these DEGs. Interestingly, a high correlation presented between any two of saponin contents, key enzyme activities and expression levels of DEGs. Taken together, the inoculation of AMF can improve the growth and saponin accumulation of P. notoginseng by strengthening the activities of key enzymes and the expression levels of encoding genes, in which the JA regulatory pathway is a key link. This study provides references for implementing ecological planting of P. notoginseng, improving saponin accumulation and illustrating the biosynthesis mechanism.

[Effect of No-tillage on Soil Aggregates in Farmland：A Meta Analysis].

In order to clarify the impact of no-tillage on the quality of farmland soil aggregates in China and promote the adaptive application of no-tillage practices， a Meta-analysis was conducted by collecting data from 116 published studies. The effects of no-tillage on aggregate size distribution， mean weight diameter （MWD）， and aggregate-associated C were studied. The results showed that compared with that under tillage， no-tillage significantly increased the proportion of macroaggregates （10.9%） and MWD （12.8%） and decreased the proportion of clay and silt （-15.5%） but had no significant effect on soil microaggregate and aggregate-associated C. The subgroup and Meta regression analysis showed that no-tillage significantly increased the proportion of macroaggregates in Northwest China （17.6%） and MWD in North China （15.4%）. In upland and clay loam， no-tillage increased MWD by 12.6% and 18.4%， respectively. The effect of no-tillage on increasing the proportion of macroaggregates increased with the soil pH. When straw returned， no-tillage significantly increased the proportion of macroaggregates （9.6%） and MWD （11.6%）， but no significant effect of no-tillage on aggregates was found after straw removal. Regarding test duration， short-term （ < 5 a） no-tillage could significantly increase the proportion of macroaggregates， whereas long-term （ > 10 a） no-tillage could improve the MWD. In different soil layers， no-tillage could only significantly improve the aggregate size distribution and MWD in topsoil （0-20 cm） but had no effect in subsoil （ > 20 cm）. In summary， no-tillage could improve aggregate size distribution and stability but had no effect on aggregate-associated C. Production region， soil properties， field management methods， and other factors should be fully considered in production practice to effectively improve the quality of soil aggregates.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Unique quinoline orientations shape the modified aptamer to sclerostin for enhanced binding affinity and bone anabolic potential.

Osteogenesis imperfecta (OI) is a rare genetic disease characterized by bone fragility and bone formation. Sclerostin could negatively regulate bone formation by antagonizing the Wnt signal pathway, whereas it imposes severe cardiac ischemic events in clinic. Our team has screened an aptamer that could promote bone anabolic potential without cardiovascular risk. However, the affinity of the aptamer is lower and needs to be improved. In the study, hydrophobic quinoline molecule with unique orientations (seven subtypes) were incorporated into key sites of a bone anabolic aptamer against sclerostin to form a modified aptamer library. Among all the quinoline modifications, 5-quinoline modification could shape the molecular recognition of modified aptamers to sclerostin to facilitate enhancing its binding to sclerostin toward the highest affinity by interacting with newly participated binding sites in sclerostin. Further, 5-quinoline modification could facilitate the modified aptamer attenuating the suppressed effect of the transfected sclerostin on both Wnt signaling and bone formation marker expression levels in vitro, promoting bone anabolism in OI mice (Col1a2+/G610C). The proposed quinoline-oriented modification strategy could shape the molecular recognition of modified aptamers to proteins to facilitate enhancing its binding affinity and therapeutic potency.

Self-reduced MXene-Metal interaction electrochemiluminescence support with synergistic electrocatalytic and photothermal effects for the bimodal detection of ovarian cancer biomarkers.

Novel two-dimensional MXene with unique optical and electrical properties has become a new focus in the field of sensing. In particular, their metallic conductivity, good biocompatibility and high anchoring ability to biomaterials make them attractive candidates. Despite such remarkable properties, there are certain limitations, such as low oxidative stability. MXene-Metal interactions are an effective strategy to maintain the long-term stability of MXene, while also improving the electrochemical activity and optical properties. Herein, a series of MXene/Ag nanocomposites including Ti3C2/Ag, Nb2C/Ag and V2C/Ag were designed based on the surface chemistry characteristics of MXene, where MXene served as the substrate for in-situ growth of silver nanoparticles via self-reduction of Ag(NH3)2+. The results showed that V2C MXene has the strongest self-reducing ability due to its multiple variable valence states, larger interlayer space and more reactive groups. Moreover, V2C/Ag exhibited unexpected oxygen reduction reaction catalytic activity and photothermal performance. In view of which, an electrochemiluminescence-photothermal (ECL-photothermal) immunosensor was developed using V2C/Ag as ECL anchor and photothermal reagent for ultrasensitive detection of Lipolysis stimulated lipoprotein receptor. This work not only provides a simple and effective synthesis method of MXene supported metal nanocomposites, but also provides more inspirations for exploring the efficient biosensing strategies.

Functionalization of the Octahydro-Binaphthol Skeleton: A Universal Strategy for Directly Constructing D-A Type Axially Chiral Biphenyl Luminescent Molecules.

D-A type axially chiral biphenyl luminescent molecules are directly constructed through ingenious functionalization of the octahydro-binaphthol skeleton without optical resolution. The circularly polarized organic light-emitting diodes based on them display remarkable circularly polarized electroluminescence emission, a high luminance of >10 000 cd m-2, a maximum external quantum efficiency of 6.6%, and an extremely low-efficiency roll-off. This work provides a universal strategy for developing efficient and diverse axially chiral biphenyl emitters.