Longitudinal assessment of plasma biomarkers for early detection of cognitive changes in subjective cognitive decline.

Background: Individuals experiencing subjective cognitive decline (SCD) are at an increased risk of developing mild cognitive impairment and dementia. Early identification of SCD and neurodegenerative diseases using biomarkers may help clinical decision-making and improve prognosis. However, few cross-sectional and longitudinal studies have explored plasma biomarkers in individuals with SCD using immunomagnetic reduction. Objective: To identify plasma biomarkers for SCD. Methods: Fifty-two participants [38 with SCD, 14 healthy controls (HCs)] underwent baseline assessments, including measurements of plasma Aß42, Aß40, t-tau, p-tau, and α-synuclein using immunomagnetic reduction (IMR) assays, cognitive tests and the Mini-Mental State Examination (MMSE). Following initial cross-sectional analysis, 39 individuals (29 with SCD, 10 HCs) entered a longitudinal phase for reassessment of these biomarkers and the MMSE. Biomarker outcomes across different individual categories were primarily assessed using the area under the receiver operating characteristic (ROC) curve. The SCD subgroup with an MMSE decline over one point was compared to those without such a decline. Results: Higher baseline plasma Aß1-42 levels significantly discriminated participants with SCD from HCs, with an acceptable area under the ROC curve (AUC) of 67.5% [95% confidence interval (CI), 52.7-80.0%]. However, follow-up and changes in MMSE and IMR data did not significantly differ between the SCD and HC groups (p > 0.05). Furthermore, lower baseline plasma Aß1-42 levels were able to discriminate SCD subgroups with and without cognitive decline with a satisfied performance (AUC, 75.0%; 95% CI, 55.6-89.1%). At last, the changes in t-tau and Aß42 × t-tau could differentiate between the two SCD subgroups (p < 0.05). Conclusion: Baseline plasma Aß42 may help identify people with SCD and predict SCD progression. The role of plasma Aß42 levels as well as their upward trends from baseline in cases of SCD that progress to mild cognitive impairment and Alzheimer's disease require further investigation.

Effect of Kinesiology Taping on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to evaluate the impact of kinesiology taping on individuals suffering from breast cancer-related lymphedema. METHODS AND METHODS: We conducted a comprehensive search in PubMed, Cochrane Library, and Embase databases, spanning from their inception date to December 20, 2023, to identify pertinent studies. Inclusion criteria comprised studies that (1) enrolled participants diagnosed with breast cancer-related lymphedema; (2) implemented kinesiology taping as the intervention; (3) incorporated either complete decongestive therapy, exercise, or sham taping as the control treatment; and (4) included clinical measurements such as the severity of lymphedema, upper limb function assessment, quality of life, and perceived comfort. RESULTS: Information was extracted from 14 randomized controlled trials (RCTs). The analyses demonstrated statistically significant improvement, indicating a preference for kinesiology taping in the outcomes of upper limb functional assessment (standardized mean difference [SMD] = -0.88, 95% confidence interval [CI]: [-1.22, -0.55]), quality of life (SMD = 0.50, 95% CI: [0.16, 0.84]), and perceived comfort (SMD = 0.85, 95% CI: [0.34, 1.36]). CONCLUSION: The findings suggest that kinesiology taping could be considered a viable option for individuals dealing with breast cancer-related lymphedema. Nevertheless, acknowledging certain limitations within this study, further confirmation of its benefits necessitates additional larger-scale and better-designed RCTs.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

A Bibliometric Analysis of the Spatial Transcriptomics Literature from 2006 to 2023.

In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields.

Injection therapy for carpal tunnel syndrome: A systematic review and network meta-analysis of randomized controlled trials.

Various injectants are available for the treatment of carpal tunnel syndrome. This systematic review and network meta-analysis was conducted to investigate the effectiveness of different injection therapies in alleviating the symptoms of carpal tunnel syndrome. Various databases were searched for relevant studies from inception until May 10, 2023. Eligible studies were identified using the patient (P), intervention (I), comparison (C), and outcomes (O) model, which involved (P) participants with carpal tunnel syndrome, (I) an intervention based on injection therapy, (C) the use of placebo or another injectant as a control treatment, and (O) the measurement of clinical and electrodiagnostic outcomes of interest. A total of 18 studies were included in the analysis. The network meta-analysis revealed that platelet-rich plasma is effective in the treatment of carpal tunnel syndrome in terms of symptom and pain relief and functional improvement in both the short and long term, whereas steroids are effective only in the short term. Additionally, injections of dextrose solution may offer long-term pain relief as well as short- and long-term symptom alleviation and functional improvement. The study findings suggest that platelet-rich plasma should be used as the first-line treatment for carpal tunnel syndrome, with dextrose and steroids serving as alternative treatment options.

Mucus Impaction Related to Postoperative Anastomosis Site Obstruction: A Rare Case.

Anastomotic stricture has an incidence rate of 6-10% and typically manifests three to six months after colorectal surgery. Immediate postoperative stricture is exceedingly rare and underreported in the literature. The possible etiology includes poor circulation, leakage, local inflammation, or infection. We report a rare case of a patient with total obstruction by mucus on the anastomosis site on postoperation day two. We used a sigmoidoscope to remove mucus material, following which the patient recovered well.

The value of urinary exosomal microRNA-21 in the early diagnosis and prognosis of bladder cancer.

Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)-21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR-21, prognostic value of miR-21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR-21, miR-4454, and urine cytology for Ta-T1 and T2-T4 stage BC were analyzed. Urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 were highly expressed in BC patients. miR-146a-5p, miR-93-5p, miR-663b, miR-21, miR-4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR-21, miR-4454, and miRNA co-diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR-21 was closely related to Tumor-Node-Metastasis staging and grading in BC patients. Urinary exosomal miR-21 had high diagnostic value for BC and Ta-T1 and T2-T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.

Stereoscopic Polymer Network for Developing Mechanically Robust Flexible Perovskite Solar Cells with an Efficiency Approaching 25.

Flexible perovskite solar cells (pero-SCs) have the potential to overturn the application scenario of silicon photovoltaic technology. However, their mechanical instability severely impedes their practical applicability, and the corresponding intrinsic degradation mechanism remains unclear. In this study, the degradation behavior of flexible pero-SCs is systematically analyzed under mechanical stress and it is observed that the structural failure first occurs in the polycrystal perovskite film, then extend to interfaces. To suppress the structural failure, pentaerythritol triacrylate, a crosslinked molecule with three stereoscopic crosslink sites, is employed to establish a 3D polymer network in both the interface and bulk perovskite. This network reduced the Young's modulus of the perovskite and simultaneously enhanced the interfacial toughness. As a result, the formation of cracks and delamination, which occur under a high mechanical stress, is significantly suppressed in the flexible pero-SC, which consequently retained 92% of its initial power conversion efficiency (PCE) after 20 000 bending cycles. Notably, the flexible device also shows a record PCE of 24.9% (certified 24.48%).

Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

BACKGROUND: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. METHODS: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). RESULTS: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased ß-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). CONCLUSIONS: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

Hyperbaric Lidocaine Aggravates Diabetic Neuropathic Pain by Targeting p38 MAPK/ERK and PINK1/Parkin-Mediated Mitophagy Signaling Pathway.

BACKGROUND: Diabetic neuropathic pain (DNP) is a complication of diabetes mellitus (DM). Hyperbaric lidocaine (HL), a local anesthetics drug, has neurotoxicity. The present study aims to study the effect and molecular mechanisms of HL on spinal nerve injury in DNP. METHODS: The DNP rat model was established through a high-fat-glucose diet in combination with Streptozotocin (STZ) administration. SB203580 and PD98059 were utilized to inhibit p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK). The mechanical paw withdrawal threshold (PWT) and the thermal paw withdrawal latency (PWL) were tested to evaluate rats' mechanical allodynia and thermal hyperalgesia. Hematoxylin-eosin (H&E) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end Labeling (TUNEL) staining were performed to evaluate the pathological changes and neuron apoptosis in spinal cord tissues of L4-5. Western blotting analysis and reverse transcription-polymerase chain reaction (RT-qPCR) assay were used to measure the levels of proteins and mRNAs, respectively. RESULTS: PWT and PWL were decreased in DNP rats with serious spinal nerve injury. HL administration downregulated the PWT and PWL and aggravated spinal nerve injury in DNP rats, but isobaric lidocaine had no effects on these changes. Meanwhile, p38 MAPK/ERK signaling and PTEN-induced kinase 1 (PINK1)-mediated mitophagy were activated in DNP, which was enhanced by HL but not isobaric lidocaine. Blocking p38 MAPK/ERK signaling could effectively attenuate HL-induced spinal nerve injury and inhibit mitophagy. CONCLUSION: In summary, HL can aggravate spinal cord tissue damage in DNP rats by inducing PINK1-mediated mitophagy via activating p38 MAPK/ERK signaling. Our data provide a novel insight that supports the potential role of p38 MAPK/ERK signaling in acting as a therapeutic target for HL-induced neurotoxicity.

Signatures of Adaptation and Purifying Selection in Highland Populations of Dasiphora fruticosa.

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.

Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

[Two kinds of percutaneous endoscopic lumbar decompression in the treatment of single level lumbar lateral recess stenosis].

OBJECTIVE: To prospectively compare the clinical efficacy and radiographic outcomes between interlaminar percutaneous endoscopic lumbar decompression(IL-PELD) and transforaminar percutaneous endoscopic lumbar decompression(TF-PELD) in the treatment of single-segment lumbar lateral recess stenosis. METHODS: From April 2018 to July 2021, 85 patients with single-segment lumbar lateral recess stenosis underment percutaneous endoscopic lumbar decompression.There were 44 males and 41 females, aged from 49 to 81 years old with an average of (65.5±8.3) years old, duration of lumbar lateral recess stenosis ranging from 3 to 83 months with an average of (26.7±16.5) months. They were divided into IL-PELD group and TF-PELD group according to the different operation methods. There were 47 patients in the IL-PELD group, including 28 males and 19 females aged from 50 to 80 yeaes old with an average age was (66.7±9.3) years old. The disease duration ranged from 3 to 65 months with an average of (25.7±15.0) months. There were 38 patients in the TF-PELD group, including 16 males and 22 females, aged from 51 to 78 years old with an average of(64.1±7.6) years old. The disease duration ranged from 4 to 73 months with an average of (27.9±18.3) months The operation time, intraoperative blood loss, intraoperative fluoroscopy, hospitalization day and complications of the two groups were recorded. Visual analogue scale (VAS) to evaluate low back pain and lower limb pain, Oswestry disability index(ODI) to evaluate lumbar function in preoperative and postoperative period(1month, 6 months and last follow-up)were recorded. the sagittal diameter of the lateral recess of the responsible intervertebral space in preoperative and 1 week after the operation were recorded. RESULTS: The operation was successfully completed in both groups without serious complications such as vascular injury, dural sac tear and nerve injury. The operation time in IL-PED group(69.3±19.3)min was significantly longer than that in TF-PELD group(57.5±14.5)min (P<0.05). There was no significant difference in the intraoperative blood loss between the two groups (P>0.05). The number of intraoperative fluoroscopy in TF-PELD group (8.8±2.6)times was significantly higher than that in IL-PED group(4.8±1.2)times (P<0.05). The hospitalization days of the two groups were not statistically significant (P>0.05). VAS for low back and lower extremity pain and ODI were (5.1±2.2), (6.9±1.3) scores and (71.4±12.6) % in IL-PELD group, and (4.7±1.8), (6.9±1.3) scores and (68.4±13.9)% in TF-PELD group. In the IL-PELD group, the VAS of low back pain was (2.4±1.5), (1.6±0.8), (1.4±0.9) scores, and the VAS of lower extremity pain was (3.0±1.2), (1.6±0.7), (1.5±1.0) scores, ODI was (32.6±11.9) %, (17.4±6.5) %, (19.3±9.3)%;In TF-PELD group, the VAS of low back pain was (2.6±1.4), (1.5±0.6), (1.4±1.0) scores, and the VAS of lower extremity pain was (2.8±1.2), (1.6±0.6), (1.5±1.2) scores, The ODI was (32.0±11.2) %, (15.0±6.1) %, and (20.0±11.3) %. The VAS and ODI of the two groups at each time point after operation were significantly improved compared with those before operation (P<0.05), but there was no statistically significant difference between the groups (P>0.05), and there was no statistically significant difference in the interaction between different time points and groups (P>0.05). At 1 week after operation, the sagittal diameter of lateral recess in both groups was significantly increased compared with that before operation (P<0.05), but there was no significant difference between the two groups at each time point (P>0.05). According to the modified Macnab criteria, IL-PELD group was rated as excellent in 24 cases, good in 19 cases and fair in 4 cases. In TF-PELD group the results were excellent in 19 cases, good in 15 cases, fair in 3 cases and poor in 1 case. There was no significant difference between the two groups (P>0.05). CONCLUSION: IL-PELD and TF-PELD can expand the lateral recess in the treatment of single level lumbar lateral recess stenosis, and have achieved good clinical effects.

Construction of phase-separated Co/MnO synergistic catalysts and integration onto sponge for rapid removal of multiple contaminants.

Wastewater treatment recycling is critical to ensure safe water supply or to overcome water shortage. Herein, we developed metallic Co integration onto MnO nanorods (MON) resulting in a phase-separated synergetic catalyst by creating more Mn(III) via the Jahn-Teller effect and oxygen vacancies and improving the redox capability of Co nanoparticles mediated by a thin carbon layer. Additionally, the N-doped surface carbon network on MON contributes to polar sites, facilitating the enrichment of contaminants around reactive sites, thereby shortening the migration of reactive oxidative species (ROS) toward contaminants. The optimized MnO@Co/C-600 exhibits superior PMS activation efficiency for bisphenol A degradation (0.463 min-1), displaying nearly a 20-fold enhancement in the rate constant compared to Mn3O4/C-600. Subsequent experiments involving variable modulation and extension were conducted to further elucidate the multiple synergistic effects. The mechanism study further confirms the synergy of ˙SO4-, ˙OH, ˙O2-, and 1O2, along with additional electron transfer pathways. The intermediates generated during degradation pathways and their toxicity to aquatic organisms were identified. Notably, a monolith integrated catalyst was explored by anchoring MnO@Co/C-600 onto a tailored melamine sponge based on Ca ion triggered crosslink tactic for the photothermal degradation of bisphenol A, tetracycline and norfloxacin, endowed with easy recovery and good stability. Furthermore, we demonstrated that the total organic carbon removal of multiple contaminants surpassed that of sole contaminants.

METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

A CuCo Bimetal Confined Hollow SiC Hybrid Photothermal Nanoreactor for the Integration of Pollutant Mineralization and Solar-Powered Water Evaporation.

Growing attention has been paid to the rational treatment of antibiotics-bearing medical wastewater. However, the complexity of polluted wastewater makes the later comprehensive treatment difficult only by the Advanced Oxidation Process technique. Therefore, the coupled water treatment techniques including contaminant mineralization and regeneration of cleanwater become very attractive. A bimetallic functional hollow nanoreactor defined as (Co@SiO2/Cu-X) was successfully constructed by coating a Cu-doped silica layer on the metal-organic framework (ZIF-67) followed by programmed calcination in nitrogen. The nanoreactor was endowed with a hollow configuration composed of mesoporous N-doping C-Silica hybrid shell encapsulated ultrafine Cu and Co metallic species. Such a configuration allows for the efficient diffusion and open reaction space of big contaminant molecules. The catalytic synergy of exposed Co-Cu bimetals and the easy accessibility of electron-rich contaminants by polar N doping sites triggered surface affinity make the optimal Co@SiO2/Cu-6 afford an excellent catalytic norfloxacin mineralization activity (7 min, kabs=0.744 min-1) compared to Cu-free Co@SiO2-6 (kabs=0.493 min-1) and Co-6 (kabs=0.378 min-1) Benefiting from the above unique advantages, Co@SiO2/Cu-6 show excellent removal performance in degrading different pollutants (carbamazepine, oxytetracycline, tetracycline, and bisphenol A) and persistent recycled stability in removing NFX. In addition, by virtue of the excellent photothermal properties, interfacial solar water evaporation application by Co@SiO2/Cu-6 was further explored to reach the regeneration of cleanwater (1.595 kg m-2 h-1, 97.51 %). The integration of pollutant mineralization and solar water evaporation by creating the monolith evaporation by anchoring the Co@SiO2/Cu-6 onto the tailored melamine sponge allows the regeneration of cleanwater (1.6 kg⋅m-2⋅h-1) and synchronous pollutant removal (NFX, 95 %, 60 min), which provides potential possibility the treatment of complicated wastewater.

DNA-modified Prussian blue nanozymes for enhanced electrochemical biosensing.

Prussian blue nanoparticles exhibit the potential to be employed in bioanalytical applications due to their robust stability, peroxidase-like catalytic functionality, straightforward synthesis, and biocompatibility. An efficient approach is presented for the synthesis of nucleic acid-modified Prussian blue nanoparticles (DNA-PBNPs), utilizing nanoparticle porosity to adsorb nucleic acids (polyT). This strategic adsorption leads to the exposure of nucleic acid sequences on the particle surface while retaining catalytic activity. DNA-PBNPs further couple with functional nucleic acid sequences and aptamers through complementary base pairing to act as transducers in biosensors and amplify signal acquisition. Subsequently, we integrated a copper ion-dependent DNAzyme (Cu2+-DNAzyme) and a vascular endothelial growth factor aptamer (VEGF aptamer) onto screen-printed electrodes to serve as recognition elements for analytes. Significantly, our approach leverages DNA-PBNPs as a superior alternative to traditional enzyme-linked antibodies in electrochemical biosensors, thereby enhancing both the efficiency and adaptability of these devices. Our study conclusively demonstrates the application of DNA-PBNPs in two different biosensing paradigms: the sensitive detection of copper ions and vascular endothelial growth factor (VEGF). These results indicate the promising potential of DNA-modified Prussian blue nanoparticles in advancing bioanalytical sensing technologies.

Low-valent-tungsten catalysis enables hydroboration of esters and nitriles.

In the research presented herein, low-valent-tungsten-catalyzed hydroboration of esters and nitriles was investigated. Aromatic and aliphatic substrates were smoothly reduced to corresponding alcohol derivatives and N,N-diborylamines in the presence of W(CO)4(NCMe)2. Valuable derivatives were conveniently accessed by introducing a further functionalization process to crude hydroboration mixtures in one pot.

Photodynamic therapy inhibits cancer progression and induces ferroptosis and apoptosis by targeting P53/GPX4/SLC7A11 signaling pathways in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor with a poor prognosis. The specific mechanism of photodynamic therapy (PDT) in treating CCA remains unclear. This study aims to investigate the mechanisms of PDT in the treatment of CCA and try to improve the therapeutic effect of PDT by intervening associated signaling pathways. METHODS: The Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of CCA cell lines following PDT. Apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. A transmission electron microscope was used to study the changes in cell mitochondria after PDT. The levels of glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), lactate dehydrogenase (LDH), and lipid peroxide (LPO) were determined. Changes in the expression of apoptosis and ferroptosis-related proteins were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Xenograft tumor models were developed to investigate the effects of PDT on tumor proliferation, apoptosis, and ferroptosis in vivo. RESULTS: PDT inhibited tumor proliferation and induced apoptosis both in vivo and in vitro. This treatment led to swelling and damage of the mitochondria in affected cells. Furthermore, ROS levels rose, accompanied by an increase in the proportion of apoptotic-positive cells. The expressions of Bax and Caspase-3 were upregulated, while the Bcl-2 was downregulated. Meanwhile, PDT triggered ferroptosis, marked by decreased expressions of GPX4 and SLC7A11, and reduced GSH levels. This was accompanied by upregulation of P53 expression and heightened levels of Fe2+, LPO, MDA, and LDH. After inducing the ferroptosis pathway, the therapeutic effect of PDT was enhanced, the tumor tissue was further reduced, and the degree of malignancy was reduced. CONCLUSION: PDT promotes apoptosis and ferroptosis of cholangiocarcinoma cells by activating the P53/SLC7A11/GPX4 signaling pathway and inhibits the growth of cholangiocarcinoma. Inducing ferroptosis can enhance the effectiveness of photodynamic therapy.

[Effect and complication among different kinds of spinal endoscopic surgery for lumbar disc herniation].

OBJECTIVE: To compare clinical efficacy and complication rate of percutaneous endoscopic transforaminal discectomy(PETD),percutaneous endoscopic interlaminar discectomy (PEID) and unilateral biportal endoscopic (UBE) in treating single-segment lumbar disc herniation(LDH). METHODS: From October 2019 to August 2021,121 LDH patients with single-segment treated by spinal endoscopy were retrospectively analyzed and divided into three groups. In PETD group,there were 48 patients,including 19 males and 29 females,aged from 18 to 72 years old with an average of (44.0±13.9) years old;3 patients with L3,4 segments,27 patients with L4,5 segments,and 18 patients with L5S1 segments. In PEID group,there were 43 patients,including 23 males and 20 females,aged from 20 to 69 years old with an average of (40.1±12.1) years old;1 patient with L3,4 segments,15 patients with L4,5 segments,and 27 patients with L5S1 segments. In UBE group,there were 30 patients,including 12 males and 18 females,aged from 29 to 72 years old with an average of (41.2±15.0) years old;1 patient with L3,4 segments,18 patients with L4,5 segments,and 11 patients with L5S1 segments. Operation time,blood loss,fluoroscopy times and complications among three groups were observed and compared. Before opertaion,3 months after operation and at the latest follow-up,visual analogue scale (VAS) was used to evaluate low back pain and lower extremity pain,Oswestry disfunction index (ODI) was used to evaluate lumbar function,and modified MacNab was used to evaluate clinical efficacy at the latest follow-up. RESULTS: All patients were performed endoscopic spinal surgery completly and were followed up for at least 12 months. One patient occurred dural sac rupture both in PETD and PEID group,and dural sac rupture was small,and there was no obvious discomfort after operation. Two patients were occurred intraoperative rupture of dural sac in UBE group. One patient was occurred cerebrospinal fluid leakage after operation,and was improved after rest in supine position and fluid rehydration. One patient without no significant postoperative discomfort. (1)There were no significant difference in operating time,blood loss and hospital stay between PETD and PEID group (P>0.05),while UBE group was higher than those of PETD and PEID group (P<0.05). There was no statistical significance in fluoroscopy times between PEID and UBE group (P>0.05),but PETD group was higher than that of PEID and UBE group (P<0.05). (2)VAS of low back pain at 3 months after operation in UBE group was higher than that in PETD and PEID group (P<0.05),but there was no significant difference between PETD and PEID group (P>0.05). At the latest follow-up,there was no significant difference in VAS of low back pain among three groups (P>0.05). (3)Lower extremity pain of VAS and ODI among 3 groups after operation were significantly improved at all time points compared with those before opertaion(P<0.05),and there were no statistical significance between groups (P>0.05),and there were no statistical significance in interaction between different time points and operation groups (P>0.05). (4) At the latest follow-up,according to the modified MacNab standard,the results of PETD group were excellent in 27 patients,good in 16 patients,moderate in 4 patients,poor in 1 patient;in PEID group,27 patients got excellent result,12 good,3 moderate,and 1 poor;in UBE group,16 patients got excellent,10 good,2 moderate,and 2 poor. There was no significant difference among three groups (χ2=0.308,P>0.05). Recurrence of lumbar disc herniation occurred in 1 patient among each three groups,symptoms were improved in 2 patients after symptomatic treatment,and 1 patient was treated in other hospitals. CONCLUSION: PETD,PEID and UBE techniques could achieve good early clinical effects in treating lumbar disc herniation with similar complication rates. Both of PETD and PEID are single-channel minimally invasive surgery,with mild intraoperative tissue damage and quick postoperative recovery; while intraoperative fluoroscopy of PETD was relatively more frequent, and PEID was more suitable for L5S1 segment;UBE is a two-channel surgery,in which the intraoperative soft tissue damage is more severe,but exposure is broad,which is more suitable for complex cases.