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In this work, a novel surface-enhanced Raman scattering (SERS) sandwich strategy biosensing platform has been established for simultaneously detecting Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Fe

Effectiveness of oseltamivir versus peramivir in influenza-infected children remains unclear. This study aims to evaluate their effectiveness in young children (ages 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV).We analyzed a cohort of 1662 young children with either IAV (N=1095) or IBV (N=567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match oseltamivir-treated versus peramivir-treated children.IAV-infected and IBV-infected children shared similar features such as influenza-associated symptoms and comorbidities at baseline. Among IAV-infected children with bacterial coinfection, the recovery rate was significantly greater in oseltamivir-treated children than in peramivir-treated children (15.6% versus 4.4%, p=0.01). The median duration of hospitalization was also shorter in oseltamivir-treated children. Among IAV-infected children without bacterial coinfection, the recovery rate was greater in oseltamivir-treated children than in peramivir-treated children (21.1% versus 3.7%, p=0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (p0.05 for both) among IBV-infected children.Oseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children.

Implant-associated infections (IAIs) caused by biofilm formation are the most devastating complications of orthopedic surgery. Statins have been commonly and safely used drugs for hypercholesterolemia for many years. Here, we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated infections. The antibacterial properties of simvastatin against

Transformed small-cell lung cancer (T-SCLC) has an extremely poor prognosis, and no remedies based on immunotherapy have been evaluated among T-SCLC patients. We retrospectively analysed the efficacy and safety of combining atezolizumab with chemotherapy for T-SCLC.Forty-seven patients harbouring EGFR mutations who developed T-SCLC were enrolled. Eleven patients who used immunotherapy were defined as the I/O group, and the remaining 36 were defined as the Non-I/O group. Clinical characteristics, pathological data, and survival outcomes were collected. RNA sequencing and whole-exome sequencing (WES) were performed for in-depth analysis.All patients received at least one line of EGFR-TKI before rebiopsy to confirm T-SCLC. Nine patients received atezolizumab-bevacizumab-carboplatin-paclitaxel (albumin-bound) (ABCP), and the remaining 2 received atezolizumab-etoposide-carboplatin (ECT) in the I/O group. The objective response rate was 73 % (8/11). The median progression-free survival (mPFS) of T-SCLC on post-transformation therapy with I/O group and Non-I/O group was 5.1 m and 4.1 m, respectively. The median post-T-SCLC overall survival of the I/O group was significantly longer than that Non-I/O group (20.2 m vs 7.9 m, P ＜ 0.01). T-SCLC harbouring EGFR L858R tended to be longer than EGFR 19del (mPFS: not reached vs 3.7 m, P = 0.11). Positive PD-L1 status was also associated with PFS benefits (mPFS: 6.0 m vs 3.7 m, P = 0.20). Furthermore, RNA sequencing revealed that expression of SFTPA1 is significantly higher in the durable clinical benefit group. WES showed that STC2 mutation is more frequently observed at the time-point immunotherapy acquired resistance. Combination therapy based on a PD-L1 inhibitor was well tolerated, and the safety profile was consistent with previously reported studies.Our study first demonstrated that a PD-L1 inhibitor combined with chemotherapy ± bevacizumab could be a potential safe option for specific SCLC-transformed patients. Subsequent studies with more patients are essential to verify the efficacy and potential biomarkers.

Paraquat is one of the most widely used nonselective herbicides in agriculture. Due to its wide use, paraquat resistant weeds have emerged and is becoming a potential threat to agriculture. The molecular mechanisms of paraquat resistance in weeds remain largely unknown. Physiological studies indicated that the impaired translocation of paraquat and enhanced antioxidation could improve paraquat resistance in plants. However, the detoxification of paraquat via active metabolism by plants has not been reported to date. Here we report that an activated expression of At1g01600 encoding the P450 protein CYP86A4 confers paraquat resistance as revealed by the gain-of-function mutant paraquat tolerance 11D (pqt11D), in which a T-DNA with four 35S enhancers was inserted at 1646 bp upstream the ATG of At1g01600. The paraquat resistance can be recapitulated in Arabidopsis wild type by overexpressing AtPQT11 (At1g01600), while its knockout mutant is hypersensitive to paraquat. Moreover, AtPQT11 also confers paraquat resistance in E. coli when overexpressed. We further demonstrate that AtPQT11 has P450 enzyme activity that converts paraquat to N-demethyl paraquat nontoxic to Arabidopsis, therefore detoxifying paraquat in plants. Taken together, our results unequivocally demonstrate that AtPQT11/ CYP86A4 detoxifies paraquat via active metabolism, thus revealing a novel molecular mechanism of paraquat resistance in plants and providing a means potentially enabling crops to resist paraquat.

Precise fabrication of biomimetic three-dimensional (3D) structure and effective neuronal differentiation under the pathological environment are the key to neural stem cell (NSC)-based spinal cord injury (SCI) therapy. In this study, we have developed a spinal cord-like bioprinted scaffold loading with OSMI-4, a small molecule O-GlcNAc transferase (OGT) inhibitor, to induce and guide the neuron differentiation of NSCs for efficient SCI repair. To achieve this, we developed a supramolecular bioink (SM bioink) consisting of methacrylated gelatin and acrylated β-cyclodextrins to load NSCs and OSMI-4. This bioink showed fast gelation and stable mechanical properties, facilitating bioprinting of functional neural scaffolds. Moreover, the weak host-guest cross-linking of the SM scaffolds significantly improved the cell-matrix interaction for the infiltration and migration of NSCs. What's more, the sustained delivery of OSMI-4 remarkably enhanced the intrinsic neuronal differentiation of the encapsulated NSCs in vitro by inhibiting Notch signaling pathway. In vivo experiment further revealed that the functional bioprinted scaffolds promoted the neuronal regeneration and axonal growth, leading to significant locomotor recovery of the SCI model rats. Together, the NSC-laden bioprinted SM scaffolds in combination with sustained release of the therapeutic agent OSMI-4 largely induced neuronal differentiation of NSCs and thus leading to efficient SCI repair. STATEMENT OF SIGNIFICANCE: Efficient neuronal differentiation of neural stem cells (NSCs) under the complex pathological microenvironment of spinal cord injury (SCI) is a major challenge of neural regeneration. By the use of a supramolecular bioink, we bioprinted a spinal cord-like scaffold loaded with NSCs and a small molecule drug OSMI-4 to significantly induce neuronal differentiation of NSCs for efficient SCI repair in vivo. The scaffolds with spinal cord-like structure can support the interaction and neuronal differentiation of NSCs by providing a dynamic matrix and a source of molecular release of OSMI-4. The influences of OSMI-4 on NSCs and its molecular mechanism were investigated for the first time in this study. Altogether, three-dimensional bioprinting fabrication of NSC- and small molecule drug-laden biomimetic construct may represent a promising therapeutic strategy for SCI repair.

To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P 0.05). In the EA + G group, SBP and DBP decreased (P 0.05), ghrelin concentrations increased (P 0.05), and the concentrations of ET-1 and TXA2 decreased (P 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P 0.05), while PF04628935 reversed these effects.EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

The present study aimed to equate the 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7) to the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscales (HADS-D,HADS-A) respectively in patients with major depressive disorder (MDD) and generate crosswalks of raw scores.As it is a single group design that adopts common-person equating method, a total of 460 patients with MDD completed the PHQ-9, GAD-7 and HADS at the same time. Rasch analysis was used to filter out invalid participants, investigate the psychometric properties of test items and participants, link the PHQ-9 and HADS-D as well as GAD-7 and HADS-A, and produce conversion tables respectively. The differences between original scores and converted scores were analyzed to validate the crosswalks.401 samples of depression part and 396 samples of anxiety part were left for final samples. Both the PHQ-9 / HADS-D and GAD-7 / HADS-A combined analysis adequately fit the unidimensional Rasch model, demonstrated acceptable reliability and item-person targeting and showed no disordering category. Slight differential item functioning across gender was found in item PHQ9 and item GAD6. The crosswalks were generated and verified to be validity.The results might be restricted to patients with MDD recruited in a single mental health center.The PHQ-9, GAD-7 and HADS depression and anxiety subscales were successfully linked, producing conversion tables that could be used for directly converting raw score from one instrument to the other.

To compare short-term follow-up outcomes after primary arthroscopy in femoroacetabular impingement syndrome (FAIS) patients with untreated central acetabular osteophytes (CAO) to a control group without CAO.A retrospective analysis was performed using data from FAIS patients who had primary arthroscopy between 2017 and 2018. The presence of CAO was confirmed arthroscopically, and there were 2 groups created. The CAO group was 1:1 propensity-score matched to a control group (without CAO) based on age, gender, body mass index (BMI), Tӧnnis grade, symptom duration before surgery, and follow-up time. Patient-reported outcomes (PROs), such as the Hip Outcome Score-Activities of Daily Living (HOS-ADL), International Hip Outcome Tool 12-component form (iHOT-12)，modified Harris Hip Score (mHHS), and visual analog scale (VAS) scores were used to evaluate the level of function included. The minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) were also calculated to determine meaningful outcome improvement. Radiographic measures, performed procedures, complications, and revision surgery were also compared and analyzed for both groups. P values less than .05 were considered statistically significant.A total of 46 hips with CAO and 46 hips without CAO were propensity matched. At the minimum final follow-up of 2 years, the CAO group had significantly lower HOS-ADL (78.8 vs 85.5; P = .008), iHOT-12 (74.8 vs 79.3; P = .019), and mHHS (78.9 vs 87.2; P = .002) scores, as compared to the CAO group. Furthermore, patients in the CAO group were significantly less likely to achieve the MCID and PASS for the mHHS score (78.3% vs 93.5%; P = .036, 58.7% vs 78.2%; P = .043, respectively). There was no change in the rate of complications (4.3% vs 0%) and revision hip arthroscopy (4.3% vs 2.2%) between the two groups at the final follow-up.This study demonstrated that surgically treated FAIS patients with CAO might experience worse short-term, patient-reported outcomes, as compared with propensity-matched patients without CAO.III, case-control study.

The development of effective uranium-removal techniques is of great significance to the environment and human health. In this work, a double potential step technique (DPST) was applied to remove U(VI) from uranium-containing wastewater using a carbon felt electrode modified by graphene oxide/phytic acid composite (GO-PA@CF). The application of DPST can inhibit water splitting and prevent GO-PA from adsorbing other interfering ions in wastewater. The GO-PA composite can effectively accelerate the electrochemical reduction rate of U(VI), which significantly improved the electrochemical deposition rate of uranium oxide. As a result, the maximum removal efficiency and maximum removal capacity of GO-PA@CF electrode reached 98.7% and 1149.3 mg/g, respectively. The removal efficiency remained 97.2% after five cycles of reuse. Moreover, the removal efficiency of GO-PA@CF electrode can reach more than 70% in simulated wastewater.

Sepsis is the leading course of morbidity and mortality in critically ill patients. This study aimed to evaluate the predictive value of the platelet aggregation for mortality in patients with sepsis. In addition, the relationship between impaired mitochondria and the platelet aggregation was explored.This was a prospective, observational cohort study. The platelet aggregation rate in response to adenosine diphosphate (ADP) was assessed. The primary outcome was 28-day mortality. Platelet mitochondrial parameters, including adenosine triphosphate(ATP), mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) opening, were measured. Platelet mitochondrial ultrastructure was observed using transmission electron microscopy.86 patients with 65 survivors and 21 non-survivors were enrolled. Platelets of non-survivors with sepsis were hyporesponsive to ADP, in terms of maximal aggregation rate (P 0.001). Receiver operating characteristic curves analysis demonstrated that the AUC estimated 28-day mortality for platelet aggregation rate was 0.814. At the optimal cut-off value of 35.8% for platelet aggregation rate, the sensitivity was 86.2% and the specificity was 66.7%. Kaplan-Meier analysis showed that a platelet aggregation rate of less than 35.8% was associated closely with poor survival. After adjusting for lactate by Cox regression analysis, platelet aggregation rate was identified as an independent predictor for the probability of 28-day mortality. Compared with survivors, non-survivors showed a significant reduction in platelet ATP and MMP-index (both P 0.001), and a remarkable increase in mPTP opening (P 0.001). ATP and MMP-index were positively correlated with platelet aggregation rate (R square=0.75, R square=0.44, respectively).Platelet aggregation rate could be an early predictive biomarker for mortality in sepsis. Impaired platelet mitochondrial activity affects platelet aggregation and correlates with the severity of sepsis.

INTRODUCTION: Video telehealth can offer people convenient, real-time access to clinicians without arranging transportation or time off work. Among people with diabetes, this study examines the association between video telehealth access and changes in HbA1c. METHODS: This longitudinal cohort study (2016–2019) used linear regression with person-level fixed effects, stratified by baseline HbA1c (last value in 2015), to examine the association between video visit access and changes in HbA1c. HbA1c values were categorized into 3 periods of video visit exposure: (1) before any video visit, (2) video visit transition year (calendar year of the first video visit), and (3) after video visits. The model compared changes in HbA1c values collected before the patient had any video visits with those collected after the transition year. Analyses was conducted in September 2020. RESULTS: Among 204,301 people with diabetes, video visit access was associated with a statistically significant reduction of 0.15 (95% CI= −0.19, −0.11) percentage points in HbA1c, with greater reductions among patients with an elevated baseline HbA1c value (−0.22 percentage points, 95% CI= −0.32, −0.11) and with no baseline HbA1c measurement (−0.39 percentage points, 95% CI= −0.71, −0.07). CONCLUSIONS: Gaining access to video telehealth was associated with reductions in HbA1c among people with diabetes. Video telehealth offers people with chronic conditions a new, convenient way to access health care, is not associated with worsening HbA1c, and may support better disease management, particularly among patients with higher baseline HbA1c.

Estimating endmembers and corresponding abundances from mixed pixels are essential steps for hyperspectral unmixing. In hyperspectral unmixing, obtaining accurate unmixing results is difficult since less prior knowledge is available. Besides, the unmixing results are influenced by noise and highly correlated endmembers, so that the obtained abundance maps exist small values which are not present in the image. In this paper, we separate each abundance map into a feature layer and a sparse layer to protect the obtained abundance maps from the above-mentioned factors. The feature layer represents the main information of the abundance map. And the sparse layer contains outliers dominated by the above-mentioned factors. In particular, we design a feature extraction regularization to describe the feature layer and use a weighted l 1 norm to describe the sparse layer. Then, under the framework of non-negative tensor factorization (NTF), we propose a novel unmixing algorithm named spatial feature extraction NTF (SFE-NTF) for hyperspectral unmixing. The proposed SFE-NTF is based on an augmented multiplicative algorithm. Experimental results on both synthetic and real hyperspectral data demonstrate that the proposed algorithm outperforms other state-of-the-art algorithms.

Neurocognitive impairment is a core feature of schizophrenia, and patients with first-episode schizophrenia (FES) are optimal candidates for cognitive remediation, but we do not know enough about the incidence, severity and longitudinal changes in neurocognitive impairment in those with FES. This study aimed to assess the neurocognitive trajectories of patients with FES and to compare the clinical and functional outcomes among those with different trajectories. A total of 562 untreated patients with FES completed a neurocognitive test battery and psychopathological and functional assessment. A total of 373 patients attended the follow-up. Group-based trajectory modelling (GBTM) was applied to identify neurocognitive trajectories. Analysis of variance and chi-square tests were conducted to compare demographic characteristics, multiple neurocognitive domains, and clinical and functional outcomes among the different subgroups. We identified three neurocognitive subgroups: preserved (n = 133), mildly to moderately impaired (n = 187) and severely impaired (n = 53). Neurocognitive function in the two impaired subgroups improved within a year but failed to reach the normal level. The processing speed followed trajectories similar to those of overall cognition. The three subgroups did not significantly differ in antipsychotic usage or clinical remission rate. The severely impaired subgroup had poorer functional outcomes than the preserved subgroup, but the mildly to moderately impaired subgroup did not. Patients with FES followed distinct neurocognitive trajectories during the first year of treatment. Patients with severe neurocognitive impairment have poorer functional outcomes, which require and are more likely to benefit from cognitive remediation. Processing speeding is a potential indicator for screening overall cognition.

The importance of structural variants (SVs) for human phenotypes and diseases is now recognized. Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed, few benchmarking procedures are available to confidently assess their performances in biological and clinical research. To facilitate the validation and application of these SV detection approaches, we established an Asian reference material by characterizing the genome of an Epstein-Barr virus (EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls. We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers, including 109× Pacific Biosciences (PacBio) continuous long reads (CLRs), 22× PacBio circular consensus sequencing (CCS) reads, 104× Oxford Nanopore Technologies (ONT) long reads, and 114× Bionano optical mapping platform, and one de novo assembly-based SV caller using CCS reads. A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing, demonstrating the robustness of our SV calls. Combining trio-binning-based haplotype assemblies, we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions (CHCRs), which covered 1.46 gigabase pairs (Gb) and 6882 SVs supported by at least one diploid haplotype assembly. Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology, disease, and clinical research.