Robust polymer hybrid and assembly materials from structure tailoring to efficient catalytic remediation of emerging pollutants.

A massive amount of toxic substances and harmful chemicals are released every day into the outer environment, imposing serious environmental impacts on both land and aquatic animals. To date, research is constantly in progress to determine the best catalytic material for the effective remediation of these harmful pollutants. Hybrid nanomaterials prepared by combining functional polymers with inorganic nanostructures got attention as a promising area of research owing to their remarkable multifunctional properties deriving from their entire nanocomposite structure. The versatility of the existing nanomaterials' design in polymer-inorganic hybrids, with respect to their structure, composition, and architecture, opens new prospects for catalytic applications in environmental remediation. This review article provides comprehensive detail on catalytic polymer nanocomposites and highlights how they might act as a catalyst in the remediation of toxic pollutants. Additionally, it provides a detailed clarification of the processing of design and synthetic ways for manufacturing polymer nanocomposites and explores further into the concepts of precise design methodologies. Polymer nanocomposites are used for treating pollutants (electrocatalytic, biocatalytic, catalytic, and redox degradation). The three catalytic techniques that are frequently used are thoroughly illustrated. Furthermore, significant improvements in the method through which the aforementioned catalytic process and pollutants are extensively discussed. The final section summarizes challenges in research and the potential of catalytic polymer nanocomposites for environmental remediation.

Modulating the Activity and SO2 Resistance of α-Fe2O3 Catalysts for NH3-SCR of NOx via Crystal Facet Engineering.

The development of Fe-based catalysts for the selective catalytic reduction of NOx by NH3 (NH3-SCR of NOx) has garnered significant attention due to their exceptional SO2 resistance. However, the influence of different sulfur-containing species (e.g., ferric sulfates and ammonium sulfates) on the NH3-SCR activity of Fe-based catalysts as well as its dependence on exposed crystal facets of Fe2O3 has not been revealed. This work disclosed that nanorod-like α-Fe2O3 (Fe2O3-NR) predominantly exposing (110) facet performed better than nanosheet-like α-Fe2O3 (Fe2O3-NS) predominantly exposing (001) facet in NH3-SCR reaction, due to the advantages of Fe2O3-NR in redox properties and surface acidity. Furthermore, the results of the SO2/H2O resistance test at a critical temperature of 250 °C, catalytic performance evaluations on Fe2O3-NR and Fe2O3-NS sulfated by SO2 + O2 or deposited with NH4HSO4 (ABS), and systematic characterization revealed that the reactivity of ammonium sulfates on Fe2O3 catalysts to NO(+O2) contributed to their improved catalytic performance, while ferric sulfates showed enhancing and inhibiting effects on NH3-SCR activity on Fe2O3-NR and Fe2O3-NS, respectively; despite this, Fe2O3-NR showed higher affinity for SO2 + O2. This work set a milestone in understanding the NH3-SCR reaction on Fe2O3 catalysts in the presence of SO2 from the aspect of crystal facet engineering.

The influence of near-infrared therapy on arteriovenous fistula patency in haemodialysis patients: A multicentre, randomised, controlled clinical trial.

BACKGROUND: Arteriovenous fistula (AVF) is the preferred vascular access for patients undergoing haemodialysis (HD). AVF malfunction remains a major clinical problem and is a significant independent risk factor for death. Although far-infrared (FIR) therapy has been shown to reduce complications and improve the patency rate of AVFs in various studies, it has been cautiously recommended by the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines for AVF care due to insufficient evidence. Therefore, it is necessary to identify more effective methods for preventing AVF dysfunction. Many in vitro studies and few clinical studies have examined the effects of near-infrared (NIR) therapy on the vasculature. This study will examine the effects of NIR therapy on AVF. METHODS: A randomised, controlled, open-label, multicentre trial will compare the effect of NIR on AVF patency after 1 year of therapy with that of a control group of patients with existing AVF. One group of patients received NIR treatment above their AVFs, whereas the control group received regular care. The primary outcome is the primary fistula patency rate within 12 months. In addition, acute changes in inflammatory, vasodilatory and haemodynamic parameters after a single treatment in the first 40 participants will be examined. This study was registered in the Clinical Trials Registry (ChiCTR2300071305) at https://register.clinicaltrials.gov/. DISCUSSIONS: This study will explore the long-term and acute effects of NIR on AVFs. The study findings will provide information that can be used to develop new technical support for the prevention of AVF dysfunction in patients undergoing haemodialysis.

Surface Coordination Environment Engineering on PtxCu1-x Alloy Catalysts for the Efficient Photocatalytic Reduction of CO2 to CH4.

Alloy catalysts have been reported to be robust in catalyzing various heterogeneous reactions due to the synergistic effect between different metal atoms. In this work, aimed at understanding the effect of the coordination environment of surface atoms on the catalytic performance of alloy catalysts, a series of PtxCu1-x alloy model catalysts supported on anatase-phase TiO2 (PtxCu1-x/Ti, x = 0.4, 0.5, 0.6, 0.8) were developed and applied in the classic photocatalytic CO2 reduction reaction. According to the results of catalytic performance evaluation, it was found that the photocatalytic CO2 reduction activity on PtxCu1-x/Ti showed a volcanic change as a function of the Pt/Cu ratio, the highest CO2 conversion was achieved on Pt0.5Cu0.5/Ti, with CH4 as the main product. Further systematic characterizations and theoretical calculations revealed that the equimolar amounts of Pt and Cu in Pt0.5Cu0.5/Ti facilitated the generation of more Cu-Pt-paired sites (i.e., the higher coordination number of Pt-Cu), which would favor a bridge adsorption configuration of CO2 and facilitate the electron transfer, thus resulting in the highest photocatalytic CO2 reduction efficiency on Pt0.5Cu0.5/Ti. This work provided new insights into the design of excellent CO2 reduction photocatalysts with high CH4 selectivity from the perspective of surface coordination environment engineering on alloy catalysts.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

The Roles of Non-coding RNA Targeting Astrocytes in Cerebral Ischemia.

Astrocytes are key targets for treating cerebral ischemia in the central nervous system. Non-coding RNAs (ncRNAs) participate in the pathological processes of astrocytes in cerebral ischemia. Recent reports suggest that ncRNAs ameliorate the outcome of cerebral ischemia by mediating astrocytes' inflammatory reaction, oxidative stress, excitotoxicity, autophagy, and apoptosis. Reconstructing cellular systems might offer a promising strategy for treating cerebral ischemia. This review briefly discusses the potential of ncRNAs as drug targets and explores the molecular regulatory mechanisms through which ncRNAs target astrocytes in cerebral ischemia. It provides an overview of the current research, discusses ncRNAs' implications as clinical markers for cerebral ischemia, and anticipates that ongoing research on ncRNAs may contribute to novel therapeutic approaches for treating this condition.

Clinical application of trio-based whole-exome sequencing in idiopathic generalized epilepsy.

PURPOSE: Idiopathic generalized epilepsies (IGEs) are a common group of genetic generalized epilepsies with high genetic heterogeneity and complex inheritance. However, the genetic basis is still largely unknown. This study aimed to explore the genetic etiologies in IGEs. METHODS: Trio-based whole-exome sequencing was performed in 60 cases with IGEs. The pathogenicity of candidate genetic variants was evaluated by the criteria of the American College of Medical Genetics and Genomics (ACMG), and the clinical causality was assessed by concordance between the observed phenotype and the reported phenotype. RESULTS: Seven candidate variants were detected in seven unrelated cases with IGE (11.7%, 7/60). According to ACMG, a de novo SLC2A1 (c.376C>T/p.Arg126Cys) variant identified in childhood absence epilepsy was evaluated as pathogenic with clinical concordance. Six variants were assessed to be uncertain significance by ACMG, but then considered causative after evaluation of clinical concordance. These variants included CLCN4 hemizygous variant (c.2044G>A/p.Glu682Lys) and IQSEC2 heterozygous variant (c.4315C>T/p.Pro1439Ser) in juvenile absence epilepsy, EFHC1 variant (c.1504C>T/p.Arg502Trp) and CACNA1H (c.589G>T/p.Ala197Ser) both with incomplete penetrance in juvenile myoclonic epilepsy, and GRIN2A variant (c.2011C>G/p.Gln671Glu) and GABRB1 variant (c.1075G>A/p.Val359Ile) both co-segregated with juvenile myoclonic epilepsy. Among them, GABRB1 was for the first time identified as potential novel causative gene for IGE. SIGNIFICANCE: Considering the genetic heterogeneity and complex inheritance of IGEs, a comprehensive evaluation combined the ACMG scoring and assessment of clinical concordance is suggested for the pathogenicity analysis of variants identified in clinical screening. GABRB1 is probably a novel causative gene for IGE, which warrants further studies.

Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.

Application of health self-management intervention program for metabolic syndrome patients in the bereaved population following the Wenchuan earthquake.

Background: The destructive Wenchuan earthquake has led to approximately 800,000 people being bereaved. In the previous cross-sectional study, we explored the long-term incidence of Metabolic Syndrome (MS) and studied its influencing factors among the bereaved population 12 years after the Wenchuan earthquake. Chronic disease self-management has become a recognized public health service. Studies have shown that demographic and genetic factors, stress, geographical environment, society, culture, dietary habits, lifestyle, and other aspects influence MS. Due to the Wenchuan earthquake being a serious stress event, the implementation of targeted interventions should be discussed further. Objectives: To verify the effect of applying a self-management intervention program for patients with MS among the bereaved population following the Wenchuan earthquake. Design: A randomized controlled trial (RCT) design was adopted. Participants: A total of 132 bereaved patients with MS following the Wenchuan earthquake constituted the sample. Methods: The study was based on the Cognitive-Phenomenological-Transaction, Chronic Disease Self-Management Program, and Patient Empowerment Conceptual Model, which combined with the latest evidence-based guidelines, were used to systematically evaluate cross-sectional results of this study that were used to construct a stress management-based health self-management intervention program and MS health self-management manual for bereaved patients with MS following the Wenchuan earthquake. In addition, we revised and completed a health self-management intervention program and health self-management manual for patients with MS by using the expert consultation method. General data were collected prior to intervention (T0). We collected the patients' MS disease-related physiological indicators before intervention (T0), after intervention (T1), and 2 months after intervention (T2). EipData3.1 software was used to input data in duplex and duplicate, and SPSS22.0 software was used for statistical analysis. Results: The variance analysis showed that the total score of healthy self-management behavior and the score of diet management, exercise management, drug management, and emotional management have intergroup effects, time effects, and group-time interaction effects (p < 0.05). When the differences between groups were further compared, we found that the total score and the score of six dimensions (excluding disease self-monitoring management) were higher than those of the control groups at T1 and T2, and the differences were statistically significant (p < 0.05). Conclusion: The intervention program of healthy self-management for patients with MS who come from bereaved families following the Wenchuan earthquake can effectively improve patients' health self-management behaviors.

A one-stop approach to diagnosing hereditary colorectal cancer in the Chinese population.

BACKGROUND AND AIM: The current procedure for identifying hereditary colorectal cancer (HCRC) is time consuming in clinical practice. This study aimed to develop a time-saving approach to diagnosing HCRC. METHODS: A total of 100 suspected HCRC patients were prospectively enrolled (cohort 1) and 116 colorectal cancer patients with DNA mismatch repair-deficient were retrospectively included (cohort 2). Next-generation sequencing (NGS) tests were performed on tumors and matched white blood cells (WBCs) or normal tissues. Using the conventional method upon WBC/normal tissue-based NGS data as a reference, the performance of the ColonCore method using tumor-only-based NGS data in predicting germline variants was explored in cohort 1 and validated in cohort 2. RESULTS: In cohort 1, the ColonCore method diagnosed 17 Lynch syndrome (LS) and 14 familial adenomatous polyposis (FAP); and by the conventional method, the cases were 16 and 10, respectively. The ColonCore method showed sensitivities of 100% in diagnosing LS (positive predictive value [PPV] 94.1%) and FAP (PPV 71.4%). Moreover, two of seven patients with multiple adenomas/polyps who did not meet existing clinical criteria for HCRC were predicted to harbor germline variants in APC and MUTYH. Additionally, the sensitivity of the ColonCore method in identifying LS patients from cohort 2 reached 85.7% with a PPV of 85.7%. CONCLUSION: The ColonCore method might be an acceptable tool for predicting germline variants associated with HCRC. Our work indicates the essentiality of NGS tests in CRC patients for precision diagnosis and treatment.

Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

HCFC1 variants in the proteolysis domain are associated with X-linked idiopathic partial epilepsy: Exploring the underlying mechanism.

BACKGROUND: HCFC1 encodes transcriptional co-regulator HCF-1, which undergoes an unusual proteolytic maturation at a centrally located proteolysis domain. HCFC1 variants were associated with X-linked cobalamin metabolism disorders and mental retardation-3. This study aimed to explore the role of HCFC1 variants in common epilepsy and the mechanism underlying phenotype heterogeneity. METHODS: Whole-exome sequencing was performed in a cohort of 313 patients with idiopathic partial (focal) epilepsy. Functional studies determined the effects of the variants on the proteolytic maturation of HCF-1, cell proliferation and MMACHC expression. The role of HCFC1 variants in partial epilepsy was validated in another cohort from multiple centers. RESULTS: We identified seven hemizygous HCFC1 variants in 11 cases and confirmed the finding in the validation cohort with additional 13 cases and six more hemizygous variants. All patients showed partial epilepsies with favorable outcome. None of them had cobalamin disorders. Functional studies demonstrated that the variants in the proteolysis domain impaired the maturation by disrupting the cleavage process with loss of inhibition of cell growth but did not affect MMACHC expression that was associated with cobalamin disorder. The degree of functional impairment was correlated with the severity of phenotype. Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated with mainly intellectual disability. CONCLUSION: HCFC1 is potentially a candidate gene for common partial epilepsy with distinct underlying mechanism of proteolysis dysfunction. The HCF-1 domains played distinct functional roles and were associated with different clinical phenotypes, suggesting a sub-molecular effect. The distinct difference between cobalamin disorders and idiopathic partial epilepsy in phenotype and pathogenic mechanism, implied a clinical significance in early diagnosis and management.

Physicochemical properties of different crystal forms of manganese dioxide prepared by a liquid phase method and their quantitative evaluation in capacitor and battery materials.

Although there are many studies on the preparation and electrochemical properties of the different crystal forms of manganese dioxide, there are few studies on their preparation by a liquid phase method and the influence of their physical and chemical properties on their electrochemical performance. In this paper, five crystal forms of manganese dioxide were prepared by using manganese sulfate as a manganese source and the difference of their physical and chemical properties was studied by phase morphology, specific surface area, pore size, pore volume, particle size and surface structure. The different crystal forms of manganese dioxide were prepared as electrode materials, and their specific capacitance composition was obtained by performing CV and EIS in a three-electrode system, introducing kinetic calculation and analyzing the principle of electrolyte ions in the electrode reaction process. The results show that δ-MnO2 has the largest specific capacitance due to its layered crystal structure, large specific surface area, abundant structural oxygen vacancies and interlayer bound water, and its capacity is mainly controlled by capacitance. Although the tunnel of the γ-MnO2 crystal structure is small, its large specific surface area, large pore volume and small particle size make it have a specific capacitance that is only inferior to δ-MnO2, and the diffusion contribution in the capacity accounts for nearly half, indicating it also has the characteristics of battery materials. α-MnO2 has a larger crystal tunnel structure, but its capacity is lower due to the smaller specific surface area and less structural oxygen vacancies. ε-MnO2 has a lower specific capacitance is not only the same disadvantage as α-MnO2, but also the disorder of its crystal structure. The tunnel size of ß-MnO2 is not conducive to the interpenetration of electrolyte ions, but its high oxygen vacancy concentration makes its contribution of capacitance control obvious. EIS data shows that δ-MnO2 has the smallest charge transfer impedance and bulk diffusion impedance, while the two impedances of γ-MnO2 were the largest, which shows that its capacity performance has great potential for improvement. Combined with the calculation of electrode reaction kinetics and the performance test of five crystal capacitors and batteries, it is shown that δ-MnO2 is more suitable for capacitors and γ-MnO2 is more suitable for batteries.

The Chronic and Acute Toxicity of Traditional Medicines Containing Terminalia chebula.

Objectives: Terminalia chebula, the main ingredient of Altan Arur 5, has been used for many years in traditional medicine. This medicine is more effective than other drugs and is used to treat chronic gastritis and gastrointestinal disorders such as peptic ulcers and esophageal reflux. Other ingredients of Altan Arur 5 are Punica granatum (pomegranate), tulip seeds, black balm, and excreta of Trogopterus xanthipes. The main ingredients of T. chebula are antibacterial and analgesic in traditional medicine. Despite having been used for many years and although many studies have been conducted on the beneficial effects of this medicine and its ingredients, the toxicity of Altan Arur 5 has not yet been elucidated. Therefore, we aimed to study the toxicity of Altan Arur 5 to ensure that it is safe to use. Methods: Acute and chronic toxicity of Altan Arur 5 were assessed in 10 Kunming mice and 8 Sprague-Dawley rats, respectively, in different doses. In the acute toxicity study, Altan Arur 5 was orally administered to Kunming mice in doses of 12 g/kg, 24 g/kg, and 48 g/kg for 14 days. In the chronic toxicity study, it was orally administered to Sprague-Dawley rats in doses of 1.25 g/kg, 2.5 g/kg, and 5 g/kg for 12 weeks. Results: No significant differences were observed in the relative organ weights for mice treated with Altan Arur 5 compared with those in the control group. Furthermore, no macro- or microstructural changes were noted in the organs of any group. Conclusion: Our toxicity testing revealed that the traditional medicine Altan Arur 5 has no toxic effects in vivo.

Comprehensive insights into the structures and dynamics of plant telomeric G-quadruplexes.

Telomeres, which are located at the ends of eukaryotic chromosomes, are crucial for genomic maintenance. Most telomeric DNA is composed of tandemly repeated guanine (G)-rich sequences, which form G-quadruplexes (G4s). The structures and dynamics of telomeric G4s are essential for telomere functioning and helpful for G4-based biosensing. However, they are far from being understood, especially for plants. In this contribution, the folding, environment-induced G4 dynamics, and protein-catalyzed unfolding of plant telomeric G4s were comprehensively studied. It was found that diverse plant telomeric sequences from land plants to green algae could fold into G4 structures. In addition, 5'-proximal ssDNA but not 3'-proximal ssDNA drove conversion of anti-parallel G4 structures to parallel structures, and both 5' and 3' ssDNA decreased the stability of G4s in dilute solution. Furthermore, molecular crowding promoted the formation of parallel structures for three-layer but not for two-layer G4s, and increased the stability of all selected G4s. Finally, AtRecQ2 helicase resolved the stable parallel structure of typical plant telomeric G4 in crowded solution, but ssDNA binding protein AtRPA did not. Furthermore, AtRecQ2 unwound the structure more efficiently in the presence of AtRPA. The results may expand our understanding on the structures and dynamics of plant telomeric G4s.

The effects of intraspecific variation on forecasts of species range shifts under climate change.

As global climate change is altering the distribution range of macroalgae across the globe, it is critical to assess its impact on species range shifts to inform the biodiversity conservation of macroalgae. Latitude/environmental gradients could cause intraspecific variability, which may result in distinct responses to climate change. It remains unclear whether geographical variation occurs in the response of species' populations to climate change. We tested this assumption using the brown alga Sargassum thunbergii, a habitat-forming macroalgae encompassing multiple divergent lineages along the Northwest Pacific. Previous studies revealed a distinct lineage of S. thunbergii in rear-edge populations. Given the phylogeographic structure and temperature gradients, we divided these populations into the southern and northern groups. We assessed the physiological responses of the two groups to temperature changes and estimated their niche differences using n-dimensional hypervolumes. A higher photosynthetic rate and antioxidative abilities were detected in the southern group of S. thunbergii than in the northern group. In addition, significant niche differentiation was detected between the two groups, suggesting the possibility for local adaptation. Given these results, we inferred that the southern group (rear-edge populations) may be more resilient to climate change. To examine climate-driven range shifts of S. thunbergii, we constructed species- and lineage-level species distribution models (SDMs). Predictions of both levels showed considerable distribution contracts along the Chinese coasts in the future. For the southern group, the lineage-level model predicted less habitat loss than the species-level model. Our results highlight the importance of considering intraspecific variation in climate change vulnerability assessments for coastal species.

Effect of Pathogenesis-Based Individualized Thrombectomy on Treatment Result and Prognosis of Acute Intracranial Large-Artery Occlusion Patients.

AIM: To explore the effect of pathogenesis-based individualised thrombectomy on the clinical results and prognoses of acute intracranial large-artery occlusion. MATERIAL AND METHODS: A total of 151 patients were included in this prospective study and divided into the control group (stent thrombectomy, 53 cases), a direct aspiration first pass technique (ADAPT) group (52 cases) and the stent group (stent thrombectomy or a combination of stent thrombectomy and ADAPT, 46 cases) based on whether stent or ADAPT was used. We compared and analysed the patients? general information, the National Institutes of Health Stroke Scale (NHISS) score at admission, the time between the end of arteriography and revascularisation, the number of thrombectomies, the modified Rankin scale (mRS) score at three months and complications in the three groups. RESULTS: Compared with the control group, the time between the end of arteriography and revascularisation in the ADAPT group was significantly reduced (p < 0.05), and the patency rate after one thrombectomy significantly increased (p < 0.05). The positive prognosis rate was significantly increased in the stent and ADAPT groups compared with the control group (p < 0.05). CONCLUSION: The application of the ADAPT technique in patients with embolism-induced cerebral infarction can reduce the time of revascularisation. The use of stents in patients with atherosclerosis-induced cerebral infarction can increase the patency rate after one thrombectomy.

Mechanistic insights into poly(C)-binding protein hnRNP K resolving i-motif DNA secondary structures.

I-motifs are four-strand noncanonical secondary structures formed by cytosine (C)-rich sequences in living cells. The structural dynamics of i-motifs play essential roles in many cellular processes, such as telomerase inhibition, DNA replication, and transcriptional regulation. In cells, the structural dynamics of the i-motif can be modulated by the interaction of poly(C)-binding proteins (PCBPs), and the interaction is closely related to human health, through modulating the transcription of oncogenes and telomere stability. Therefore, the mechanisms of how PCBPs interact with i-motif structures are fundamentally important. However, the underlying mechanisms remain elusive. I-motif structures in the promoter of the c-MYC oncogene can be unfolded by heterogeneous nuclear ribonucleoprotein K (hnRNP K), a PCBP, to activate its transcription. Here, we selected this system as an example to comprehensively study the unfolding mechanisms. We found that the promoter sequence containing 5 C-runs preferred folding into type-1245 to type-1234 i-motif structures based on their folding stability, which was further confirmed by single-molecule FRET. In addition, we first revealed that the c-MYC i-motif structure was discretely resolved by hnRNP K through two intermediate states, which were assigned to the opposite hairpin and neighboring hairpin, as further confirmed by site mutations. Furthermore, we found all three KH (hnRNP K homology) domains of hnRNP K could unfold the c-MYC i-motif structure, and KH2 and KH3 were more active than KH1. In conclusion, this study may deepen our understanding of the interactions between i-motifs and PCBPs and may be helpful for drug development.

A novel cuproptosis-related molecular pattern and its tumor microenvironment characterization in colorectal cancer.

Cuproptosis, or copper-induced cell death, has been reported as a novel noncanonical form of cell death in recent times. However, the potential roles of cuproptosis in the alteration of tumor clinicopathological features and the formation of a tumor microenvironment (TME) remain unclear. In this study, we comprehensively analyzed the cuproptosis-related molecular patterns of 1,274 colorectal cancer samples based on 16 cuproptosis regulators. The consensus clustering algorithm was conducted to identify cuproptosis-related molecular patterns and gene signatures. The ssGSEA and ESTIMATE algorithms were used to evaluate the enrichment levels of the infiltrated immune cells and tumor immune scores, respectively. The cuproptosis score was established to assess the cuproptosis patterns of individuals with principal component analysis algorithms based on the expression of cuproptosis-related genes. Three distinct cuproptosis patterns were confirmed and demonstrated to be associated with distinguishable biological processes and clinical prognosis. Interestingly, the three cuproptosis patterns were revealed to be consistent with three immune infiltration characterizations: immune-desert, immune-inflamed, and immune-excluded. Enhanced survival, activation of immune cells, and high tumor purity were presented in patients with low cuproptosisScore, implicating the immune-inflamed phenotype. In addition, low scores were linked to high tumor mutation burden, MSI-H and high CTLA4 expression, showing a higher immune cell proportion score (IPS). Taken together, our study revealed a novel cuproptosis-related molecular pattern associated with the TME phenotype. The formation of cuproptosisScore will further strengthen our understanding of the TME feature and instruct a more personalized immunotherapy schedule in colorectal cancer.

The Correlation between the Use of the Proton Pump Inhibitor and the Clinical Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

Background: To determine if the use of the Proton Pump Inhibitors (PPI) impacts the clinical efficacy of Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC), a meta-analysis was conducted. Method: Eleven studies from PubMed, EMBASE, Cochrane Library, Web of Science, and other databases up to May 2022, were selected. The pertinent clinical outcomes were assessed by applying the Progression-free survival (PFS), Overall Survival (OS), Hazard Ratio (HR), and 95% Confidence Interval (CI). Result: This study included eleven articles containing 7,893 NSCLC patients. The result indicated that PPI use was dramatically related to poor OS (HR: 1.30 [1.10-1.54]), and poor PFS (HR: 1.25 [1.09-1.42]) in case of patients treated with ICIs. With regard to the subgroup analysis, PPI use was dramatically associated with poor OS (Europe: HR = 1.48 [1.26, 1.74], Worldwide: HR = 1.54 [1.24, 1.91]), and poor PFS (Europe: HR = 1.36 [1.18, 1.57], Worldwide: HR = 1.34 [1.16, 1.55]) in patients from Europe and multi-center studies across the world, poor OS in patients with age less than or equal to 65 (HR = 1.56 [1.14, 2.15]), poor PFS in patients aged more than 65 (HR = 1.36 [1.18, 1.57]), poor OS for patients receiving with PD-1 (HR = 1.37 [1.04, 1.79]), poor PFS for patients receiving with PD-L1 (HR = 1.33 [1.19, 1.49]), and poor OS (-30: HR = 1.89 [1.29, 2.78], ±30: HR = 1.44 [1.27, 1.64]) and poor PFS (-30: HR = 1.51 [1.11, 2.05], ±30: HR = 1.32 [1.20, 1.45]) for patients who received PPI at 30 days before and/or after starting the ICIs treatment. Conclusion: Our meta-analysis indicated that PPI combined with ICIs in the treatment of NSCLC patients could result in poor OS and PFS. PPI use should be extremely cautious in clinical practices to avoid the impact on the efficacy of the ICIs.