Sustainable 3D printing by reversible salting-out effects with aqueous salt solutions.

Achieving a simple yet sustainable printing technique with minimal instruments and energy remains challenging. Here, a facile and sustainable 3D printing technique is developed by utilizing a reversible salting-out effect. The salting-out effect induced by aqueous salt solutions lowers the phase transition temperature of poly(N-isopropylacrylamide) (PNIPAM) solutions to below 10 °C. It enables the spontaneous and instant formation of physical crosslinks within PNIPAM chains at room temperature, thus allowing the PNIPAM solution to solidify upon contact with a salt solution. The PNIPAM solutions are extrudable through needles and can immediately solidify by salt ions, preserving printed structures, without rheological modifiers, chemical crosslinkers, and additional post-processing steps/equipment. The reversible physical crosslinking and de-crosslinking of the polymer through the salting-out effect demonstrate the recyclability of the polymeric ink. This printing approach extends to various PNIPAM-based composite solutions incorporating functional materials or other polymers, which offers great potential for developing water-soluble disposable electronic circuits, carriers for delivering small materials, and smart actuators.

Modulating confinement space in metal-organic frameworks enables highly selective indole C3-formylation.

Here, Selective C3-formylation of indole was achieved under mild conditions using a metal-organic framework (MOF) catalyst. The confined reaction space within the MOF pores effectively suppressed undesired side reactions and promoted the formation of the targeted product by controlling the reaction pathway. Density functional theory (DFT) calculations corroborated the experimental observations.

Response of antioxidation and immunity to combined influences of pH and ammonia nitrogen in the spotted babylon (Babylonia areolata).

Spotted babylon were exposed to three different pH levels (7.0, 8.0 and 9.0) and four different concentrations of ammonia nitrogen (0.02, 1.02, 5.10 and 10.20 mg/L) in seawater to determine their acute toxicity and physiological responses to environmental fluctuation. The study evaluated four antioxidant enzymes: catalase (CAT), alkaline, superoxide dismutase (SOD), peroxidase (POD) and glutathione peroxidase (GSH-PX), and two immunoenzymes: acid phosphatase (ACP) and phosphatase (AKP). Over time, the immunoenzyme activity was significantly affected by pH and ammonia nitrogen concentration. After being exposed to pH and ammonia nitrogen, the spotted babylon showed signs of unresponsiveness to external stimuli, reduced vitality, slow movement, and an inability to maintain an upright position. Over time, the spotted babylon exhibited a trend of increasing and then decreasing GSH-PX, CAT, and SOD activities to adapt to the changing environment and enhance its immunity. On the contrary, the POD and ACP activities exhibited a decreasing trend initially, followed by an increasing trend over time and the AKP activity showed a gradual increase with time. The combined effect of pH and ammonia was found to be stronger than the effect of either factor alone. The interaction between pH and ammonia increased the activity of the spotted babylon antioxidant enzymes, induced oxidative stress, and reduced the ability of the spotted babylon's non-specific immune system to reverse it. Thus, the reverse-back of the spotted babylon was higher when pH and ammonia stress were dual than when pH or ammonia were single-factor stresses. The study results will establish a theoretical basis for analyzing the risk of multiple factors to the spotted babylon, and also enrich the basic information about the shellfish immune system.

Systemic immune-inflammation index as a novel predictor of major adverse cardiovascular events in patients undergoing percutaneous coronary intervention: a meta-analysis of cohort studies.

BACKGROUND: The Systemic Immune-Inflammation Index (SII), a novel marker of inflammation based on neutrophil, platelet, and lymphocyte counts, has demonstrated potential prognostic value in patients undergoing percutaneous coronary intervention (PCI). Our aim was to assess the correlation between the SII and major adverse cardiovascular events following percutaneous coronary intervention. METHODS: We searched PubMed, Web of Science, Embase, and The Cochrane Library from inception to November 20, 2023, for cohort studies investigating the association between SII and the occurrence of MACEs after PCI. Statistical analysis was performed using Revman 5.3, with risk ratios (RRs) and 95% confidence intervals (CIs) as relevant parameters. RESULTS: In our analysis, we incorporated a total of 8 studies involving 11,117 participants. Our findings revealed that a high SII is independently linked to a increased risk of MACEs in PCI patients (RR: 2.08,95%CI: 1.87-2.32, I2 = 42%, p < 0.00001). Additionally, we demonstrated the prognostic value of SII in all-cause mortality, heart failure, and non-fatal myocardial infarction. CONCLUSIONS: Elevated SII may serve as a potential predictor for subsequent occurrence of MACEs in patients undergoing PCI. TRIAL REGISTRATION: Our protocol was registered in PROSPERO (registration number: CRD42024499676).

The latest emerging drugs for the treatment of diabetic cardiomyopathy.

INTRODUCTION: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus involving multiple pathophysiologic mechanisms. In addition to hypoglycemic agents commonly used in diabetes, metabolism-related drugs, natural plant extracts, melatonin, exosomes, and rennin-angiotensin-aldosterone system are cardioprotective in DCM. However, there is a lack of systematic summarization of drugs for DCM. AREAS COVERED: In this review, the authors systematically summarize the most recent drugs used for the treatment of DCM and discusses them from the perspective of DCM pathophysiological mechanisms. EXPERT OPINION: We discuss DCM drugs from the perspective of the pathophysiological mechanisms of DCM, mainly including inflammation and metabolism. As a disease with multiple pathophysiological mechanisms, the combination of drugs may be more advantageous, and we have discussed some of the current studies on the combination of drugs.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Xinnaotongluo liquid protects H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3.

Xinnaotongluo liquid has been used to improve the clinical symptoms of patients with myocardial infarction. However, the molecular mechanism of Xinnaotongluo liquid is not completely understood. H9c2 cells exposed to hypoxia/reoxygenation (H/R) was used to simulate damage to cardiomyocytes in myocardial infarction in vitro. The biological indicators of H9c2 cells were measured by cell counting kit-8, enzyme linked immunoabsorbent assay, and western blot assay. In H/R-induced H9c2 cells, a markedly reduced murine double minute 2 (MDM2) was observed. However, the addition of Xinnaotongluo liquid increased MDM2 expression in H/R-induced H9c2 cells. And MDM2 overexpression strengthened the beneficial effects of Xinnaotongluo liquid on H9c2 cells from the perspective of alleviating oxidative damage, cellular inflammation, apoptosis and ferroptosis of H/R-induced H9c2 cells. Moreover, MDM2 overexpression reduced the protein expression of p53 and Six-Transmembrane Epithelial Antigen of Prostate 3 (STEAP3). Whereas, STEAP3 overexpression hindered the function of MDM2-overexpression in H/R-induced H9c2 cells. Our results insinuated that Xinnaotongluo liquid could protect H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3, which provide a potential theoretical basis for further explaining the working mechanism of Xinnaotongluo liquid.

Realizing Stable Perovskite Solar Cells with Efficiency Exceeding 25.6% Through Crystallization Kinetics and Spatial Orientation Regulation.

Organic-inorganic hybrid perovskites have emerged as highly promising candidates for photovoltaic applications, owing to the exceptional optoelectronic properties and low cost. Nonetheless, the performance and stability of solar cells suffer from the defect states of perovskite films aroused by non-optically active phases and non-centralized crystal orientation. Herein, a versatile organic molecule, Hydantoin, to modulate the crystallization of perovskite, is developed. Benefiting from the diverse functional groups, more spatially oriented perovskite films with high crystallinity are formed. This enhancement is accompanied by a conspicuous reduction in defect density, yielding efficiency of 25.66% (certified 25.15%), with superb environmental stability. Notably, under the standard measurement conditions (ISOS-L-1I), the maximum power point (MPP) output maintains 96.8% of the initial efficiency for 1600 h and exhibits excellent ion migration suppression. The synergistic regulation of crystallization and spatial orientation offers novel avenues for propelling perovskite solar cell (PSC) development.

Integrated analyses reveal unexpected complex inversion and recombination in RH genes.

Phenotype D-- is associated with severe hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. It is typically caused by defective RHCE genes. In this study, we identified a D-- phenotype proband and verified RH phenotypes of other six family members. However, inconsistent results between the phenotypic analysis and Sanger sequencing revealed intact RHCE exons with no mutations in the D-- proband, but the protein was not expressed. Subsequent Oxford Nanopore Technologies whole-genome sequencing of the proband revealed an inversion with ambiguous breakpoints in the intron 2 and intron 7 and copy number variation loss in the RHCE gene region. Given that the RHCE gene is highly homologous to the RHD gene, we conducted a comprehensive analysis using Pacific Biosciences long-read target sequencing, Bionano optical genome mapping, and targeted next-generation sequencing. Our findings revealed that the proband had two novel recombinant RHCE haplotypes, RHCE*Ce(1-2)-D(3-10) and RHCE*Ce(1-2)-D(3-10)-Ce(10-8)-Ce(3-10), with clear-cut breakpoints identified. Furthermore, the RH haplotypes of the family members were identified and verified. In summary, we made a novel discovery of hereditary large inversion and recombination events occurring between the RHD and RHCE genes, leading to lack of RhCE expression. This highlights the advantages of using integrated genetic analyses and also provides new insights into RH genotyping.

Restoration of virulence in the attenuated Candid#1 vaccine virus requires reversion at both positions 168 and 427 in the envelope glycoprotein GPC.

Live-attenuated virus vaccines provide long-lived protection against viral disease but carry inherent risks of residual pathogenicity and genetic reversion. The live-attenuated Candid#1 vaccine was developed to protect Argentines against lethal infection by the Argentine hemorrhagic fever arenavirus, Junín virus. Despite its safety and efficacy in Phase III clinical study, the vaccine is not licensed in the US, in part due to concerns regarding the genetic stability of attenuation. Previous studies had identified a single F427I mutation in the transmembrane domain of the Candid#1 envelope glycoprotein GPC as the key determinant of attenuation, as well as the propensity of this mutation to revert upon passage in cell culture and neonatal mice. To ascertain the consequences of this reversion event, we introduced the I427F mutation into recombinant Candid#1 (I427F rCan) and investigated the effects in two validated small-animal models: in mice expressing the essential virus receptor (human transferrin receptor 1; huTfR1) and in the conventional guinea pig model. We report that I427F rCan displays only modest virulence in huTfR1 mice and appears attenuated in guinea pigs. Reversion at another attenuating locus in Candid#1 GPC (T168A) was also examined, and a similar pattern was observed. By contrast, virus bearing both revertant mutations (A168T+I427F rCan) approached the lethal virulence of the pathogenic Romero strain in huTfR1 mice. Virulence was less extreme in guinea pigs. Our findings suggest that genetic stabilization at both positions is required to minimize the likelihood of reversion to virulence in a second-generation Candid#1 vaccine.IMPORTANCELive-attenuated virus vaccines, such as measles/mumps/rubella and oral poliovirus, provide robust protection against disease but carry with them the risk of genetic reversion to the virulent form. Here, we analyze the genetics of reversion in the live-attenuated Candid#1 vaccine that is used to protect against Argentine hemorrhagic fever, an often-lethal disease caused by the Junín arenavirus. In two validated small-animal models, we find that restoration of virulence in recombinant Candid#1 viruses requires back-mutation at two positions specific to the Candid#1 envelope glycoprotein GPC, at positions 168 and 427. Viruses bearing only a single change showed only modest virulence. We discuss strategies to genetically harden Candid#1 GPC against these two reversion events in order to develop a safer second-generation Candid#1 vaccine virus.

Targeted next-generation sequencing and long-read HiFi sequencing provide novel insights into clinically significant KLF1 variants.

BACKGROUND: Krüppel-like factor 1 (KLF1), a crucial erythroid transcription factor, plays a significant role in various erythroid changes and haemolytic diseases. The rare erythrocyte Lutheran inhibitor (In(Lu)) blood group phenotype serves as an effective model for identifying KLF1 hypomorphic and loss-of-function variants. In this study, we aimed to analyse the genetic background of the In(Lu) phenotype in a population-based sample group by high-throughput technologies to find potentially clinically significant KLF1 variants. RESULTS: We included 62 samples with In(Lu) phenotype, screened from over 300,000 Chinese blood donors. Among them, 36 samples were sequenced using targeted Next Generation Sequencing (NGS), whereas 19 samples were sequenced using High Fidelity (HiFi) technology. In addition, seven samples were simply sequenced using Sanger sequencing. A total of 29 hypomorphic or loss-of-function variants of KLF1 were identified, 21 of which were newly discovered. All new variants discovered by targeted NGS or HiFi sequencing were validated through Sanger sequencing, and the obtained results were found to be consistent. The KLF1 haplotypes of all new variants were further confirmed using clone sequencing or HiFi sequencing. The lack of functional KLF1 variants detected in the four samples indicates the presence of additional regulatory mechanisms. In addition, some samples exhibited BCAM polymorphisms, which encodes antigens of the Lutheran (LU) blood group system. However, no BCAM mutations which leads to the absence of LU proteins were detected. CONCLUSIONS: High-throughput sequencing methods, particularly HiFi sequencing, were introduced for the first time into genetic analysis of the In(Lu) phenotype. Targeted NGS and HiFi sequencing demonstrated the accuracy of the results, providing additional advantages such as simultaneous analysis of other blood group genes and clarification of haplotypes. Using the In(Lu) phenotype, a powerful model for identifying hypomorphic or loss-of-function KLF1 variants, numerous novel variants have been detected, which have contributed to the comprehensive understanding of KLF1. These clinically significant KLF1 mutations can serve as a valuable reference for the diagnosis of related blood cell diseases.

Pan-Cancer Analysis Reveals Disulfidoptosis-Associated Genes as Promising Immunotherapeutic Targets: Insights Gained from Bulk Omics and Single-Cell Sequencing Validation.

Disulfidoptosis, a novel form of cell death, is distinct from other well-known cell death mechanisms. Consequently, a profound investigation into disulfidoptosis elucidates the fundamental mechanisms underlying tumorigenesis, presenting promising avenues for therapeutic intervention. Comprehensive analysis of disulfidoptosis-associated gene (DRG) expression in pan cancer utilized TCGA, GEO, and ICGC datasets, including survival and Cox-regression analyses for prognostic evaluation. We analyzed the association between DRG expression and both immune cell infiltration and immune-related gene expression using the ESTIMATE and TISDIB datasets. We obtained our single-cell RNA sequencing (scRNA-seq) data from the GEO repository. Subsequently, we assessed disulfidoptosis activity in various cell types. Evaluation of immune cell infiltration and biological functions was analyzed via single-sample gene set enrichment (ssGSEA) and gene set variation analysis (GSVA). For in vitro validation experiments, the results from real-time PCR (RT-qPCR) and Western blot were used to explore the expression of SLC7A11 in hepatocellular carcinoma (HCC) tissues and different cancer cell lines, while siRNA-mediated SLC7A11 knockdown effects on HCC cell proliferation and migration were examined. Expression levels of DRGs, especially SLC7A11, were significantly elevated in tumor samples compared to normal samples, which was associated with poorer outcomes. Except for SLC7A11, DRGs consistently exhibited high CNV and SNV rates, particularly in HCC. In various tumors, DRGs were negatively associated with DNA promoter methylation. TME analyses further illustrated a negative correlation of DRG expression with ImmuneScore and StromalScore and a positive correlation with tumor purity. Our analysis unveiled diverse cellular subgroups within HCC, particularly focusing on Treg cell populations, providing insights into the intricate interplay of immune activation and suppression within the tumor microenvironment (TME). These findings were further validated through RT-qPCR, Western blot analyses, and immunohistochemical analyses. Additionally, the knockdown of SLC7A11 induced a suppression of proliferation and migration in HCC cell lines. In conclusion, our comprehensive pan-cancer analysis research has demonstrated the significant prognostic and immunological role of disulfidoptosis across a spectrum of tumors, notably HCC, and identified SLC7A11 as a promising therapeutic target.

Dipole Field-Driven Organic-Inorganic Heterojunction for Highly Sensitive Ultraviolet Photodetector.

Developing high-performance organic-inorganic ultraviolet (UV) photodetectors (PDs) has attracted considerable attention. However, this development has been hindered due to poor directional charge-transfer ratios in transport layers, excessive costs, and an ambiguous underlying mechanism. To tackle these challenges, we constructed a heterojunction of economic Mg-doped ZnO (MgZnO) nanorods and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) [PEDOT:PSS (P:P)] that utilizes dipole field-driven spontaneous polarization to enhance photogenerated charge kinetics. As a result, the proposed heterojunction has an improved noise equivalent power of 3.16 × 10-11 W Hz-1/2), a normalized detection rate (D*) of 8.96 × 109 jones, and external quantum efficiency comparable to other ZnO-based devices. Notably, the prepared PDs showed a photocurrent of 4.8 × 10-3 µA under a faint UV light having an intensity of 1 × 10-5 W cm-2, exceeding the performance of the most state-of-the-art ZnO-based UV sensors. The introduction of Mg into ZnO is responsible for the high performance, as it causes a lattice mismatch and distortion of the Mg-doped ZnO unit cell. It results in improved dipole movement and the creation of a dipole field, accelerating the directional electron-transfer process. Using a dipole field to manipulate the migration and transport of photogenerated carriers represents a promising approach for achieving outstanding performance in UV PDs.

Somatostatin receptor subtype 2A expression and genetics in 184 paragangliomas: a single center retrospective observational study.

PURPOSE: Adrenal and extra-adrenal paragangliomas (PGLs) are a group of neuroendocrine tumors (NETs) with strong heterogeneity, which often express somatostatin receptor subtype 2 A (SSTR2A). However, the association between SSTR2A expression and genetic status of PGLs remains unclear. The purpose of the study was to identify whether various pathogenic variants (PVs) had an impact on SSTR2A expression in PGLs. METHODS: This retrospective study included 184 patients with pathologically confirmed PGLs. The immunohistochemical expression of SSTR2A were studied in 184 tumors and PVs were tested in 159 tumor samples. Clinical and genetic data were compared in SSTR2A positive and negative PGLs. RESULTS: SSTR2A was positive in 63.6% (117/184) of all tumors. PGLs with negative SSTR2A were more likely to be extra-adrenal (37.0% vs 18.0%; P = 0.005) and exhibited a considerably greater proportion of PVs (75.4% vs. 49.0%; P = 0.001) than those with positive SSTR2A. Compared to those without PVs, a higher proportion of PGLs with PVs in cluster 1B (P = 0.004) and cluster 2 (P = 0.004) genes, especially VHL (P = 0.009), FGFR1 (P = 0.010) and HRAS (P = 0.007), were SSTR2A negative. SSTR2A was positive in all tumors (4/4) with SDHx PVs and in 87.5% (7/8) of metastatic PGLs. CONCLUSIONS: SSTR2A negativity was correlated with extra-adrenal tumor location and PVs in cluster 1B and cluster 2 genes such as VHL, FGFR1 and HRAS. Immunohistochemistry of SSTR2A should be taken into consideration in the personalized management of PGLs.

Fully genotyping and screening of clinically important blood-group antigens by MALDI TOF mass spectrometry.

Several molecular biology methods are available for high-throughput blood typing. In this study, we aimed to build a high-throughput blood-group genetic screening system for high-frequency blood-group antigen-negative rare-blood groups in donors and patients. The amplification primers for all blood-type gene fragments involving the selected alleles were designed for detection. Single-base extend primers were also designed based on specific loci. DNA fragments were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) for the last nucleotide identification of amplification products in the extend step. The accuracy was verified by known samples. Thirty-six random samples were detected by serological tests and sequencing to verify the system stability. After verification, according to the collected known rare-blood-type samples, all the alleles designed to be detected matched with the validated single-nucleotide polymorphisms. The verification tests showed that all genotyping results of the random samples were in accordance with the findings of serotyping and sequencing. Then, 1258 random donor samples were screened by the built typing system after the verification. Three Fy(a-) and four s- were screened out in 1258 random blood samples. The multiple polymerase chain reaction-based MS detection system can be used in rare-blood-type screening with good accuracy and stability.

Zn Anode Surviving Extremely Corrosive Polybromide Environment with Alginate-Graphene Oxide Hydrogel Coating.

Zinc-bromine (Zn-Br) redox provides a high energy density and low-cost option for next-generation energy storage systems, and polybromide diffusion remains a major issue leading to Zn anode corrosion, dendrite growth, battery self-discharge and limited electrochemical performance. A dual-functional Alginate-Graphene Oxide (AGO) hydrogel coating is proposed to prevent polybromide corrosion and suppress dendrite growth in Zn-Br batteries through negatively charged carboxyl groups and enhanced mechanical properties. The battery with anode of plain zinc coated with AGO (Zn]AGO) survives a severely corrosive environment with higher polybromide concentration than usual without a membrane, and achieves 80 cycles with 100% Coulombic and 80.65% energy efficiencies, four times compared to plain Zn anode. The promising performance is comparable to typical Zn-Br batteries using physical membranes, and the AGO coating concept can be well adapted to various Zn-Br systems to promote their applications.

Glial Fibrillary Acidic Protein as a Potential Indicator for Symptomatic Intracranial Hemorrhage in Acute Ischemic Patients Undergoing Endovascular Thrombectomy.

Background: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association between levels of GFAP in the bloodstream and the occurrence of sICH. Methods: Between June 2019 and May 2023, 142 consecutive AIS patients undergoing EVT at Stroke Center and 35 controls from the Physical Examination Center were retrospectively included. The levels of GFAP in the bloodstream were quantified using enzyme-linked immunosorbent assay prior to endovascular treatment (T1) and 24 h after the procedure (T2). The identification of sICH was based on the Heidelberg Bleeding Classification. Results: Serum GFAP levels at T1 in AIS patients were significantly higher than those in the controls (0.249 [0.150-0.576] versus 0.065 [0.041-0.110] ng/mL, p = 0.001), and there was a notably elevation in GFAP levels at T2 compared to T1 (3.813 [1.474, 5.876] versus 0.249 [0.150-0.576] ng/mL, p = 0.001). Of the 142 AIS patients, 18 (14.5%) had sICH after EVT. Serum GFAP levels at T2 showed significant associations with sICH in both the unadjusted model (OR 1.513, 95% CI 1.269-1.805, p = 0.001) and multivariable adjusted model (OR 1.518, 95% CI 1.153-2.000, p = 0.003). Furthermore, the addition of GFAP at T2 to conventional model resulted in a significant enhancement of risk reclassification for sICH (integrated discrimination improvement [IDI] 0.183, 95% CI 0.070-0.295, p = 0.001). Conclusion: Serum GFAP levels were notably increased in AIS patients 24 h after EVT. Elevated GFAP levels were correlated to an elevated risk of sICH. GFAP could potentially serve as a dependable indicator for sICH in AIS individuals who treated with EVT.

Influence of verbal instruction on gait training in Parkinson's disease: a randomized controlled trial.

OBJECTIVE: Verbal instruction is one of the most commonly used methods that therapists use to correct walking pattern for people with Parkinson's disease (PD). This study aimed to compare the long-term training effects of two different verbal instructions that either asked the participants to 'take big steps' or 'strike the ground with the heel' on walking ability in individuals with PD. DESIGN: Forty-five participants with PD were randomized into the big-step (BIG) or heel strike (HS) group. The participants underwent 12 sessions of treadmill and overground gait training. Throughout the interventions, the BIG group received an instruction to 'take big steps,' while the HS group received an instruction to 'strike the ground with your heel.' The primary outcome was gait performance, including velocity, stride length, cadence, and heel strike angle. The participants were assessed before, immediately after, and 1-month after training. RESULTS: Both groups showed significant improvements in gait performance after training. The HS group showed continuous improvements in velocity and stride length during the follow-up period; however, the BIG group showed slightly decreased performance. CONCLUSION: A verbal instruction emphasizing heel strike can facilitate long-term retention of walking performance in people with PD.

A Phase 1b Clinical Trial of Neoadjuvant Radio-immunotherapy for Esophageal Squamous Cell Cancer.

PURPOSE: Neoadjuvant chemoradiotherapy is the recommended treatment for patients with resectable esophageal cancer but is associated with a higher incidence of adverse effects. Given the efficacy of immunotherapy, we propose a chemotherapy-free regimen of neoadjuvant radio-immunotherapy (NRIT) to balance therapeutic efficacy and potential side effects or overtreatment. METHODS AND MATERIALS: In this phase 1b clinical trial, we assessed the safety and efficacy of NRIT in esophageal squamous cell cancer. The enrolled patients received 41.4 Gy of radiation and 4 cycles of 240 mg of toripalimab injection before surgery. The primary endpoint was treatment-related adverse events and the secondary endpoints were pathologic complete response and major pathologic response. Immunohistochemistry and multiplex immunofluorescence staining were used to evaluate the tumor microenvironment before and after neoadjuvant treatment. RESULTS: Of the 22 patients enrolled, 19 underwent R0 surgery. One patient discontinued neoadjuvant immune therapy due to experiencing a grade 3 treatment-related adverse event. Three patients did not undergo surgery due to tumor progression or side effects. Among the patients who underwent surgery, 3 patients experienced serious complications shortly after surgery. Upon pathologic evaluation, the pathologic complete response and major pathologic response rates were 47.4% and 68.4%, respectively. CONCLUSIONS: The NRIT regimen is safe and feasible for patients with esophageal squamous cell cancer.

A novel homozygous splice-site mutation of JK gene leads to Jk(a-b-) phenotype.

OBJECTIVES: This study aimed to investigate the molecular mechanism of the Jk(a-b-) phenotype in a Chinese transfusion patient. BACKGROUND: Many different mutation types relating to Jk(a-b-) phenotype have been reported. However, the splice-site mutation is relatively rare and the related functional verification is lacking. MATERIALS AND METHODS: In this study, the blood sample was collected from a transfusion patient with the Jk(a-b-) phenotype. Serotyping was performed using routine serological methods. The exons sequences and coding regions of the JK gene were amplified using polymerase chain reaction and directly sequenced. To perform a minigene splicing assay, the intronic mutation sequences were cloned into a pSPL3 splice reporting vector. The splicing reporter minigene assay was performed in HEK 293T cells. RESULTS: The Jk(a-b-) phenotype of the blood sample was identified through serological testing. Sequencing results revealed that the sample had a novel homozygous splice-site mutation JK*02N (NM_015865.7: c.663+3A>C). Further analysis, including cDNA sequencing and minigene splicing assay, confirmed that the novel splice-site mutation resulted in exon skipping. Interestingly, different numbers of exons being skipped were obtained by the two methods. CONCLUSION: This study revealed a novel homozygous splicing-site mutation associated with the Jk(a-b-) phenotype in Chinese population. Our results emphasise the importance of the in vitro functional method minigene splicing assay, while also acknowledging its potential limitations when compared to cDNA sequencing.