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The spread of SARS-CoV-2 keeps threatening human life and health, and small-molecule antivirals are in demand. The main protease (M

The incidence rate of colorectal polyps in children has gradually increased in recent years. It is still unclear whether endoscopic mucosal resection (EMR) can be performed in children with colorectal polyps as well as their incidences of post-polypectomy bleeding and recurrence. This retrospective study was performed to explore the feasible of EMR in children with colorectal polyps and analyze the risk factors of post-polypectomy bleeding and recurrence.Patients aged younger than 18 years diagnosed with colorectal polyps and received EMR for polypectomy between January 2017 and December 2021 were included in this study. The baseline data of included patients were retrospectively collected. All complications related to polypectomy were recorded during follow up via telephone, internet, or outpatient department, including post-polypectomy bleeding, perforation and polyp recurrence. Patients with and without post-polypectomy complications were divided into 2 groups. The risk factors of post-polypectomy bleeding and polyp recurrence were analyzed using multivariable logistic regression models after adjusting potential risk factors using univariable regression models.A total of 589 patients were included in this retrospective study. There were 333 male patients and 256 female patients, and their average age was 4.4±1.9 years old. The average diameter of their polyps was 8.4±2.8 mm, and 542 (92.0%) polyps presented as pedunculated lesions. A total of 540 (91.7%) polyps were diagnosed as juvenile polyps and 509 (86.4%) patients had only 1 polyp. There were a total of 75 cases of post-polypectomy complications (12.7%). The most common complication was early post-polypectomy bleeding (5.3%), followed by polyp recurrence (3.7%). Post-polypectomy bleeding occurred the most on the third and fourth day after EMR polypectomy. Larger polyps (OR =1.742, P0.001), sessile lesions (OR =3.150, P=0.019), and multiple polyps (OR =4.372, P=0.003) were identified to be related to the incidence of post-polypectomy bleeding. Besides, sessile lesions (OR =3.887, P=0.026) were identified as the main risk factor and older patients (OR =0.606, P=0.004) had lower potential for post-polypectomy recurrence.More attention should be paid to large, sessile, and multiple polyps during the procedure of EMR in children. The small number of patients in this study limits further analysis of results and a large sample study should be performed.

Cyclic adenosine monophosphate (cAMP) signaling integrates information from diverse G-protein-coupled receptors, such as neuromodulator receptors, to regulate pivotal biological processes in a cellular-specific and subcellular-specific manner. However, in vivo cellular-resolution imaging of cAMP dynamics remains challenging. Here, we screen existing genetically encoded cAMP sensors and further develop the best performer to derive three improved variants, called cAMPFIREs. Compared with their parental sensor, these sensors exhibit up to 10-fold increased sensitivity to cAMP and a cytosolic distribution. cAMPFIREs are compatible with both ratiometric and fluorescence lifetime imaging and can detect cAMP dynamics elicited by norepinephrine at physiologically relevant, nanomolar concentrations. Imaging of cAMPFIREs in awake mice reveals tonic levels of cAMP in cortical neurons that are associated with wakefulness, modulated by opioids, and differentially regulated across subcellular compartments. Furthermore, enforced locomotion elicits neuron-specific, bidirectional cAMP dynamics. cAMPFIREs also function in Drosophila. Overall, cAMPFIREs may have broad applicability for studying intracellular signaling in vivo.

We disclosed herein a straightforward photochemical method for the construction of phenanthridines containing a synthetically useful succinate unit. The reaction occurred under visible-light irradiation with cheap eosin Y Na as photoredox catalyst and a diazo compound as the succinate precursor. Under the optimal reaction conditions, a wide range of phenanthridines were obtained in moderate to good yields. Note that the succinate units in the final heterocycles could be easily transformed into many valuable structures, such as γ-butyrolactone, dihydrofuran-2(3

Dual leucine zipper kinase (DLK) plays a pivotal role in the development, degeneration, and regeneration of neurons. DLK can regulate gene expression post-transcriptionally, but the underlying mechanism remains poorly understood. The Drosophila DLK, Wallenda (Wnd), regulates the expression of Down syndrome cell adhesion molecule (Dscam) to control presynaptic arbor growth. This regulation is mediated by the 3′ untranslated region (3′UTR) of Dscam mRNA, which suggests that RNA binding proteins (RBPs) mediate DLK function. We performed a genome-wide cell-based RNAi screen of RBPs and identified the cytoplasmic poly(A)-binding protein, pAbp, as an RBP that mediates Wnd-induced increase in Dscam expression. Genetic analysis shows that Wnd requires pAbp for promoting presynaptic arbor growth and for enhancing Dscam expression. Our analysis revealed that Dscam mRNAs harbor short poly(A) tails. We identified a region in Dscam 3′UTR that specifically interacts with pAbp. Removing this region significantly reduced Wnd-induced increase in Dscam expression. These suggest that a noncanonical interaction of PABP with the 3′UTR of target transcripts is essential for DLK functions. SIGNIFICANCE STATEMENT The kinase DLK plays key roles in a multitude of neuronal responses, including axon development, neurodegeneration, and nerve injury. Previous studies show that DLK acts via mRNAs to regulate protein synthesis, but how DLK does so is poorly understood. This study demonstrates that DLK regulates the synthesis of Dscam through the poly(A)-binding protein PABP-C. Whereas PABP-C is known as a general translational activator, our study shows that DLK-mediated Dscam expression involves a noncanonical interaction between PABP-C and the Dscam mRNA, which leads to a selective regulation of Dscam translation by PABP-C. Thus, our study provides novel insights into the mechanisms that underlie the function of DLK and regulation of gene expression of PABP-C.

During mammalian neocortex development, nascent pyramidal neurons migrate along radial glial cells and overtake earlier-born neurons to terminate at the front of the developing cortical plate (CP), leading to the outward expansion of the CP border. While much has been learned about the cellular and molecular mechanisms that underlie the migration of pyramidal neurons, how migrating neurons bypass the preceding neurons at the end of migration to reach their final positions remains poorly understood. Here, we report that Down syndrome cell adhesion molecule (DSCAM) is required for migrating neurons to bypass their postmigratory predecessors during the expansion of the upper cortical layers. DSCAM is a type I transmembrane cell adhesion molecule. It has been linked to Down syndrome through its location on Chromosome 21 trisomy and to autism spectrum disorders through loss-of-function mutations. Ex vivo time-lapse imaging demonstrates that DSCAM is required for migrating neurons to bypass their postmigratory predecessors, crossing the CP border to expand the upper cortical layers. In DSCAM-deficient cortices, migrating neurons stop prematurely under the CP border, leading to thinner upper cortical layers with higher neuronal density. We further show that DSCAM weakens cell adhesion mediated by N-cadherin in the upper cortical plate, allowing migrating neurons to traverse the CP border and expand the CP. These findings suggest that DSCAM is required for proper migratory termination and final positioning of nascent pyramidal neurons, which may provide insight into brain disorders that exhibit thinner upper layers of the cerebral cortex without neuronal loss. SIGNIFICANCE STATEMENT Newly born neurons in the developing mammalian neocortex migrate outward toward the cortical surface, bypassing earlier born neurons to expand the developing cortex. How migrating neurons bypass the preceding neurons and terminate at the front of the expanding cortex remains poorly understood. We demonstrate that Down syndrome cell adhesion molecule (DSCAM), linked to Down syndrome and autism spectrum disorder, is required by migrating neurons to bypass their postmigratory predecessors and terminate migration in the outwardly expanding cortical layer. Migrating neurons deficient in DSCAM stop prematurely, failing to expand the cortex. We further show that DSCAM likely mediates migratory termination by weakening cell adhesion mediated by N-cadherin.

Neural networks are groups of interconnected neurons, which collectively give rise to emergent neural activities and functions that cannot be explained by the activity of single neurons. How neural networks are assembled is poorly understood. While all aspects of neuronal development are essential for the assembly of a functional neural network, we know little about high-level principles that govern neural network assembly beyond the basic steps of neuronal development. In this review, I use vertebrate spinal motor columns, Drosophila larval motor circuit, and the lamination in the vertebrate inner retina to highlight the spatial codes, temporal codes, and cell adhesion codes for neural network assembly. Nevertheless, these examples only show preliminary connections between neural network development and their functions. Much needs to be done to understand the molecular mechanisms that underlie the assembly of functional neural networks.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings. This resource describes a collection of neurons from a variety of light microscopy-based datasets, which can serve as a gold standard for testing automated tracing algorithms, as shown by comparison of the performance of 35 algorithms.

A multi-objective and multi-step performance parameters prediction scheme based on SCINet for optical network equipment is proposed. It not only saves 83.96% of training time on average, but also has high reliability.

We propose a failure data augmentation scheme based on time-series generation adversarial networks with real equipment performance data of optical networks and verify that the augmented failure sample data is similar to real failure data.

We propose a novel technique to measure Kerr nonlinearity in a hollow-core fiber based on nonlinear phase shift estimation by high-order QAM transmission. The measured n2,Kerr of the NANF-5 medium is -23 m2/W.

The classification of renal neoplasms continues to evolve with novel, emerging, and provisional entities being described constantly. Biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC) associated with somatic NF2 mutations is one such new renal entity and is considered as a provisional category of RCC due to its very limited data. To provide further support for the newly proposed entity, we identified three additional cases of BHP RCC, with clinicopathological, immunohistochemical, and various molecular analyses. There were 2 males and 1 female, aged 65, 56, and 69 years, respectively. The neoplasms were unencapsulated, and all had a characteristic biphasic appearance of smaller cells clustering around basement membrane material within larger acini, forming pseudorosettes or a glomeruloid pattern. Hyalinized sclerotic stroma and psammoma bodies were abundant in two cases and focally present in one case. Focal areas of a less distinctive appearance were also noted; one additionally had an elongated tubular pattern in the myxoid stroma that is reminiscent of mucinous tubular and spindle cell carcinoma; one consisted solid alveolar architectures of epithelioid clear cells, bearing some resemblance to clear cell RCC. The neoplasms did not have a distinctive immunohistochemistry (IHC) profile, though all labeled for vimentin and CK7. Targeted DNA sequencing revealed that one case harbored a pathogenic somatic frameshift mutation in the NF2 gene, which was further confirmed by Sanger sequencing. The other two cases lacked NF2 mutations and instead demonstrated NF2 promoter methylation by methylation-specific polymerase chain reaction. Subsequent IHC assessment showed loss of expression of NF2 in all 3 cases, which evaluated NF2 status at the protein level. According to RNA sequencing-based clustering analysis, the 3 cases formed a distinct group with a shared specific transcriptional profile different from that of other established renal tumor types. In addition, phosphate inositide 3-kinase (PI3K)/AKT pathway was enriched significantly and on the top of all enriched pathways. Clinically, one patient developed bone metastases and died of disease two years after diagnosis. The other two patients had no evidence of recurrence or metastases, at 4- and 5-year follow-up. These findings not only validate previously described clinicopathological features but also expand the potentially genetic alterations and available clinical outcome data.

Objective: To evaluate the effectiveness and safety of using off-the-shelf “Octopus” technique to treat ruptured or symptomatic thoracoabdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PRAAA). Methods and Results: All cases who underwent “Octopus” technique from May 2016 to May 2019 at our center were retrospectively analyzed. A total of 10 cases (8 males) were included. The mean age was 54.5±14.2 years (range: 31–80 years). Eight cases presented as aneurysm rupture or impending rupture accepted emergency repair. Technical success, defined by placement of all endografts as planned, was achieved in all cases. A total of 30 target visceral branches were successfully cannulated, 9 celiac arteries were covered intentionally. Intraoperative endoleak was observed in 6 patients, all of them were gutter leak. During hospital stay, there was no death, no side branch occlusion or spinal cord ischemia. Median follow-up was 30 months (range: 12–50 months). One patient died of lung cancer at 14-month follow-up. There was no secondary endoleak. The primary endoleak were found spontaneously resolved in 3 cases at 7 days, 3-month, and 1-year imaging. One persistent endoleak totally resolved after sealing of gutter spaces at 4-month follow-up. The other 2 persistent endoleak decreased during follow-up, which are still under observation. The branch patency rate was 90.3% (28/31). All the 3 occluded branches were renal arteries. Branch occlusion occurred in 2 cases at 1-month follow-up and 1 case at 2-year follow-up, but renal insufficiency was not observed in these cases. Obvious aneurysm sac shrinkage (≥5 mm) was observed in all cases. The aneurysm size shrunk from 7.6±1.9 to 5.5±1.4 cm. No spinal cord ischemia occurred during follow-up. Conclusion: Treatment of ruptured TAAA and PRAAA with “Octopus” technique is feasible and safe for high surgical risk patients in the absence of fenestrated and branched devices. The long-term clinical outcomes needed to be investigated.

Quantifying animal behavior is important for biological research. Identifying behaviors is the prerequisite of quantifying them. Current computational tools for behavioral quantification typically use high-level properties such as body poses to identify the behaviors, which constrains the information available for a holistic assessment. Here we report LabGym, an open-source computational tool for quantifying animal behaviors without this constraint. In LabGym, we introduce “pattern image” to represent the animal’s motion pattern, in addition to “animation” that shows all spatiotemporal details of a behavior. These two pieces of information are assessed holistically by customizable deep neural networks for accurate behavior identifications. The quantitative measurements of each behavior are then calculated. LabGym is applicable for experiments involving multiple animals, requires little programming knowledge to use, and provides visualizations of behavioral datasets. We demonstrate its efficacy in capturing subtle behavioral changes in diverse animal species.

BACKGROUND Studies have shown that mobile applications (apps) have the potential to serve as a non-pharmacological intervention for dementia care and improve the quality of life of people living with dementia (PLwD) and their informal caregivers. However, little is known about the needs and privacy aspects of these mobile apps in dementia care. OBJECTIVE This review sought to understand the landscape of existing mobile apps in dementia care for PLwD and their caregivers with respect to app features, usability testing, privacy and security. METHODS An extensive database search was conducted. Records were independently screened, and two reviewers abstracted data. Findings were summarized and tabulated based on each research aim. RESULTS Forty-four studies were included in this review, with 39 published after 2015. Fifty apps were included in the study, with more apps developed for PLwD as end-users compared to caregivers. Eight themes that contributed to app usability were found. Five methods (questionnaires, interviews, observations, logging, and focus groups) were used to evaluate usability. The reliability of usability testing may be improved by using objective measures. There was little focus on the privacy and security aspects, including the data transfer and protection, of mobile applications for PLwD. CONCLUSIONS This review highlighted key issues related to usability, privacy and security of existing mobile apps for PLwD and their caregivers. To advance future work, our findings provide a guiding framework to app developers/researchers for their privacy policy generation, app development strategy, and usability testing of their app. CLINICALTRIAL CRD42020216141 INTERNATIONAL REGISTERED REPORT RR2-10.1159/000514838

Herein, an I2-catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom-economy. This protocol not only represents the first molecular-iodine-catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine-ynamides involving distinctively different C(sp3)-C(sp3) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2. Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5-exo-dig cyclization/rearrangement process.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R10L4 was endowed with significant inhibitory activity towards wild-type HIV-1 (EC50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC50 = 0.017 μmol/L, SI = 13,055), E138K (EC50 = 0.017 μmol/L, SI = 13,123) and Y181C (EC50 = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R10L4 was characterized with significantly reduced cytotoxicity (CC50 = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R10L4 and HIV-1 RT. Additionally, R10L4 presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development. ispartof: Acta Pharm Sin B vol:13 issue:6 pages:2747-2764 ispartof: location:Netherlands status: published

We realized 420-Gbit/s/channel WDM coherent transmission over 4,000-km ULAF utilizing a novel well-expandable Ring-Wise Neural Network equalizer (RW-NNE) targeted to PS-64QAM signals. Results show that our RW-NNE with 25.3%-lower complexity outperforms normal NNE by 25% reach improvement.

To quantify the effect of multiple sclerosis (MS) on spatiotemporal gait characteristics accounting for disability severity and fall classification.MEDLINE (1946-August 2018), Allied and Complementary Medicine Database (1985-2018 August), and PsycINFO (1806-August 2018) were searched for terms on MS and gait.Dual independent screening was conducted to identify observational, cross-sectional studies that compared adults with MS grouped according to Expanded Disability Status Scale (EDSS) level or fall history, reported on spatiotemporal gait characteristics, and were published in English. The search retrieved 5891 results, of which 12 studies satisfied the inclusion criteria.Two authors worked independently to extract and verify data on publication details, study methodology, participant characteristics, gait outcomes, conclusions, and limitations. Risk of bias was assessed using the QualSyst critical appraisal tool. A random-effects meta-regression and meta-analysis were conducted on pooled data.All studies received quality ratings of very good to excellent and collectively examined 1513 individuals with MS. With every 1-point increase in EDSS, significant changes (P.05) were observed in gait speed (-0.12 m/s; 95% confidence interval (CI), 0.08-0.15), step length (-0.04 m; 95% CI, 0.03-0.05), step time (+0.04 seconds; 95% CI, 0.02-0.06), step time variability (+0.009 seconds; 95% CI, 0.003-0.016), stride time (+0.08 seconds; 95% CI, 0.03-0.12), cadence (-4.4 steps per minute; 95% CI, 2.3-6.4), stance phase duration (+0.8% gait cycle; 95% CI, 0.1-1.5), and double support time (+3.5% gait cycle; 95% CI, 1.5-5.4). Recent fallers exhibited an 18% (95% CI, 13%-23%) reduction in gait speed compared with nonfallers (P.001).This review provides the most accurate reference values to-date that can be used to assess the effectiveness of MS gait training programs and therapeutic techniques for individuals who differ on disability severity and fall classification. Some gait adaptations could be part of adopting a more cautious gait strategy and should be factored into the design of future interventions.

Background Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor with distinct histologic and immunologic features. PEComas that originate in the bladder are extremely rare clinically, with only 35 cases reported in the English literature thus far. Here, we report a case of bladder PEComa resection by transurethral en bloc resection of bladder tumor (ERBT). Case presentation A 66-year-old female with a history of poorly controlled type 2 diabetes with associated complications of frequent urinary tract infections presented to our hospital for a routine physical examination. Outpatient ultrasound examination revealed a strong echogenic mass of approximately 1.5 × 1.3 × 1.3 cm in size on the posterior wall of the bladder. The enhanced computed tomography and enhanced magnetic resonance imaging after admission both suggested a well-defined isolated nodular mass on the posterior wall of the bladder with significant enhancement on the enhanced scan. The tumor was successfully and completely resected by ERBT. Postoperative pathological examination and immunohistochemical results confirmed the mass was a bladder PEComa. No tumor recurrence was observed in the six-month postoperative follow-up. Conclusion Bladder PEComa is an extremely rare mesenchymal tumor of the urinary system. When imaging and cystoscopy reveal a nodular mass with an abundant blood supply in the bladder, PEComa should be included in the differential diagnosis of bladder tumors. Surgical resection is currently the primary option for the treatment of bladder PEComa. For a solitary, pedunculated, narrow-based, small-sized bladder PEComa, resection of the tumor by ERBT was a safe and feasible approach in our patient and may be considered for similar cases in the future.

The objective of this study was to investigate the cardiac protective effect of low-to-moderate intensity exercise training and the role of the Wnt signaling pathway in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto (WKY) rats were randomly divided into 5 groups, namely hypertensive control (SHR-S), hypertensive plus exercise training (SHR-E), normal blood pressure control (WKY-S), normal blood pressure plus exercise training (WKY-E) and SHR-E plus Wnt agonist (SHR-E-Wnt). The rats in SHR-E and WKY-E groups underwent low-to-moderate intensity swimming for 16 weeks, and the rats in SHR-E-Wnt group were injected with Wnt agonist 1 through tail vein 4 weeks before the end of swimming. The blood pressure of rats was measured every week. After exercise training, the left ventricular wall thickness and ejection function were measured by ultrasound cardiogram, myocardial structure and collagen fiber changes were observed by HE staining and Masson staining, and the expression levels of β-catenin and Dishevelled-1 (DVL-1) mRNA and protein in left ventricular myocardium were detected by real-time fluorescence quantitative PCR and Western blot, respectively. The results showed that the body weight was decreased (P0.05), blood pressure was increased (P0.01), heart weight and ventricular wall thickness were increased (P0.01), and the left ventricular ejection function was decreased (P0.05) in SHR-S group compared with those in WKY-S group. In addition, the heart structure was damaged, collagen fibers were significantly increased, and the mRNA and protein expressions of β-catenin and DVL-1 in the left ventricle were significantly up-regulated in SHR-S group compared with those in WKY-S group (P0.01). Compared with those in SHR-S group, the body weight of SHR-E group did not change significantly (P 0.05), but the blood pressure was decreased (P 0.01), heart weight and ventricular wall thickness were diminished, ejection function was increased (P 0.01), myocardial structure injury was significantly improved, collagen fibers were significantly reduced, and mRNA and protein expression levels of β-catenin and DVL-1 in the left ventricle were significantly down-regulated (P0.01) in SHR-E group. Importantly, exercise-induced antihypertensive and cardioprotective effects in SHR were blunted by Wnt agonist. These results suggest that low-to-moderate intensity exercise training exerts cardioprotective effects in SHR, possibly through inhibiting the Wnt signaling pathway.

The musculoskeletal system plays a critical role in providing the physical scaffold and movement to the mammalian body. Musculoskeletal disorders severely affect mobility and quality of life and pose a heavy burden to society. This new field of musculoskeletal tissue engineering has great potential as an alternative approach to treating large musculoskeletal defects. Natural and synthetic polymers are widely used in musculoskeletal tissue engineering owing to their good biocompatibility and biodegradability. Even more promising is the use of natural and synthetic polymer composites, as well as the combination of polymers and inorganic materials, to repair musculoskeletal tissue. Therefore, this review summarizes the progress of polymer-based scaffolds for applications of musculoskeletal tissue engineering and briefly discusses the challenges and future perspectives.

Diabetic wounds always have puzzled patients and caused serious social problems. Due to the lack of local blood vessels, severe hypoxia is generated in the defect area, which is an essential reason for the difficulty of wound healing. We have constructed a photocatalytic oxygen evolution and antibacterial biomimetic repair membrane to solve the problems of wound repair. A scanning electron microscope and transmission electron microscope characterized the biomimetic repair membrane. The oxygen evolution of the biomimetic membrane was tested by an oxygen meter. The excellent antibacterial performance of the biomimetic repair membrane was also verified by co-culture with Staphylococcus aureus and Escherichia coli. It was confirmed that the expression of collagen and HIF1-α in fibroblasts was significantly increased in vitro. And the mitochondrial activity of the vascular and nerve was increased considerably. In vivo, the healing time of diabetes wounds treated with the biomimetic repair membrane was significantly reduced, the collagen and the number of pores were increased considerably, and vascular regeneration was enhanced. The biomimetic repair membrane has an excellent performance in photocatalytic oxygen evolution and antibacterial and can significantly promote the repair of diabetes wounds. This will provide a promising treatment for diabetes wound repair.

The lockdown due to COVID-19 created a rare opportunity to examine the nonlinear responses of secondary aerosols, which are formed through atmospheric oxidation of gaseous precursors, to intensive precursor emission reductions. Based on unique observational data sets from six supersites in eastern China during 2019-2021, we found that the lockdown caused considerable decreases (32-61%) in different secondary aerosol components in the study region because of similar-degree precursor reductions. However, due to insufficient combustion-related volatile organic compound (VOC) reduction, odd oxygen (Ox = O3 + NO2) concentration, an indicator of the extent of photochemical processing, showed little change and did not promote more decreases in secondary aerosols. We also found that the Chinese provinces and international cities that experienced reduced Ox during the lockdown usually gained a greater simultaneous PM2.5 decrease than other provinces and cities with an increased Ox. Therefore, we argue that strict VOC control in winter, which has been largely ignored so far, is critical in future policies to mitigate winter haze more efficiently by reducing Ox simultaneously.

Several TSC1/2- or MTOR -mutated eosinophilic renal tumor subsets are emerging, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumors (EVTs) and low-grade oncocytic tumors (LOTs). "Unclassified renal tumors with TSC/MTOR mutations" ( TSC -mt RCC-NOS) do not meet the criteria for other histomolecular subtypes. Whether these tumors represent a continuum of 1 TS C/ MTOR -mutation-associated disease is unknown.We evaluated the clinicopathologic and IHC profiles of 39 eosinophilic renal tumors with targeted DNA sequencing-confirmed TSC/MTOR mutations. Twenty-eight of these, plus 6 ChRCC, 5 RO, 5 ccRCC, 7 MiT RCC and 6 normal renal tissues, were profiled transcriptionally by RNA-seq.The 39 cases were reclassified based on morphological and IHC features as ESC RCC (12), EVT (9), LOT, (8) and TSC -mt RCC-NOS (10). The mutation profiles demonstrated consistency; ESC RCCs (12/12) had TSC mutations, and most LOTs (7/8) had MTOR mutations. Ten TSC -mt RCC-NOSs exhibited heterogeneous morphology, arising a differential diagnosis with other renal tumors, including MiT RCC, PRCC and epithelioid PEComa. RNA sequencing-based clustering segregated ESC RCC, EVT and LOT from each other and other renal tumors, indicating expression profile-level differences. Most TSC- mt RCC-NOSs (6/7) formed a mixed cluster with ESC RCC, indicating similar expression signatures; one TSC- mt RCC-NOS with unusual biphasic morphology clustered with EVT.We expanded the TSC/MTOR -associated eosinophilic renal tumor morphologic spectrum, identified gene mutation characteristics, and highlighted differential diagnosis challenges, especially with MiT RCC. ESC RCC, EVT, and LOT having distinct expression profiles. TSC -mt RCC-NOS may cluster with recognized TSC/MTOR -associated entities.

People living with dementia (PLwD) often exhibit behavioral and psychological symptoms, such as episodes of agitation and aggression. Agitated behavior in PLwD causes distress and increases the risk of injury to both patients and caregivers. In this paper, we present the use of a multi-modal wearable device that captures motion and physiological indicators to detect agitation in PLwD. We identify features extracted from sensor signals that are the most relevant for agitation detection. We hypothesize that combining multi-modal sensor data will be more effective to identify agitation in PLwD in comparison to a single sensor. The results of this unique pilot study are based on 17 participants’ data collected during 600 days from PLwD admitted to a Specialized Dementia Unit. Our findings show the importance of using multi-modal sensor data and highlight the most significant features for agitation detection.

With the increasing demand of bandwidth, a higher capacity communication system is required for short-reach optical link. Intensity modulation/direct detection (IM-DD) is considered as a reasonable method, due to its low cost and power consumption. In the aspect of digital signal processing (DSP), discrete Fourier transform-spread (DFT-s) precoding can be used to reduce peak to average power ratio (PAPR) and average the noise among the subcarriers. In addition, probabilistic shaping (PS) turns out to further increase the system capacity. We experimentally demonstrated a 200 Gbit/s single λ dual band DMT transmission with a spectrum efficiency (SE) of 6.29 bit/s/Hz. The achievable information rate (AIR) of the proposed dual band signal increases about 30 Gbit/s compared with that of single band signal. Moreover, single-sideband (SSB) signal and signal with guard band are implemented to mitigate the frequency selective fading of optical fiber chromatic dispersion (CD). The performance of these two methods are quite closed for short reach transmission. Considering the signal-signal beat interference (SSBI) introduced by the SSB signal, an extra Volterra filter is applied in DSP. Besides, an extra optical filter is required to generate the SSB signal.

Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous studies have shown that the protein level of the Drosophila homolog of DSCAM determines the size of presynaptic terminals. However, whether the triplication of DSCAM contributes to presynaptic development in DS remains unknown. Here, we show that DSCAM levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In the Ts65Dn mouse model for DS, where DSCAM is overexpressed due to DSCAM triplication, GABAergic innervation of PyNs by basket and chandelier interneurons is increased. Genetic normalization of DSCAM expression rescues the excessive GABAergic innervations and the increased inhibition of PyNs. Conversely, loss of DSCAM impairs GABAergic synapse development and function. These findings demonstrate excessive GABAergic innervation and synaptic transmission in the neocortex of DS mouse models and identify DSCAM overexpression as the cause. They also implicate dysregulated DSCAM levels as a potential pathogenic driver in related neurological disorders.

The variations of single event transient (SET) pulse width of high-LET heavy ion irradiation in 16-nm-thick bulk silicon fin field-effect transistor (FinFET) inverter chains with different driven strengths are measured at different temperatures. Three-dimensional (3D) technology computer-aided design simulations are carried out to study the SET pulse width and saturation current varying with temperature. Experimental and simulation results indicate that the increase in temperature will enhance the parasitic bipolar effect of bulk FinFET technology, resulting in the increase of SET pulse width. On the other hand, the increase of inverter driven strength will change the layout topology, which has a complex influence on the SET temperature effects of FinFET inverter chains. The experimental and simulation results show that the device with the strongest driven strength has the least dependence on temperature.

Although luminescent indium(III) based halide perovskites have been widely investigated, the study of emissive indium(III) halide hybrids is limited. Three indium(III) chloride hybrids based on a bpym ligand were synthesized, namely [EPy]2[InCl4(bpym)InCl4]·DMF (1), [EPy]2[InCl4(bpym)InCl4] (2), and [BPy]2[InCl4(bpym)InCl4] (3) (EPy = N-ethylpyridinium; BPy = N-butylpyridinium; bpym = 2,2′-bipyrimidine). They all exhibit a zero-dimensional structure, in which the ligand bpym interconnects two [InCl4]− to form a [InCl4(bpym)InCl4]2− anion that is further charge-compensated by the corresponding pyridinium cations. This is the first time using bpym to coordinate with an In atom. At 298 K, 1 exhibits a weak emission at 600 nm while 2 and 3 exhibit emissions peaking at 500 nm and 540 nm, respectively. Interestingly, the DMF solvent molecule in 1 can be removed by heating, thus resulting in the structural transformation of 1 into 2 together with a photoluminescence (PL) change. Density functional theory (DFT) calculations confirm that halogen-to-ligand charge-transfer (HLCT) occurs in the emission process. To the best of our knowledge, this is the first report on PL of ionic indium(III) halide hybrids incorporating organic ligands.

Three isomorphic ionic bismuth(III) halides were synthesized, utilizing 2,2′-bipyridyl-1,1′-dioxide (bp2do) as the organic ligand decorated on the halobismuthate(III) moieties, namely, [Ammim][BiBr4(bp2do)] (1, Ammim = 1-allyl-2,3-dimethylimidazolium), [Ammim][BiCl4(bp2do)] (2) and [Amim][BiCl4(bp2do)] (3, Amim = 1-allyl-3-methylimidazolium). They all crystallize in the space group of Pca21 with a similar supramolecular packing mode. However, the average adjacent Bi–Bi distances are slightly different, that is 1 > 2 > 3. Moreover, they possess different phosphorescence quantum yields (QYs) with 0.38% for 1, 27.83% for 2 and 34.76% for 3. Note that the QY of 3 remains the highest for bp2do-based halobismuthate hybrids. Their phosphorescence originates from the organic ligand bp2do, in which an inorganic-to-organic charge transfer (IOCT) process exists, as confirmed by density functional theory (DFT) calculations. The three compounds possess X-ray scintillation properties. Eventually, a WLED could be fabricated by mixing commercial nitride red phosphor with cyan-emitting 3. This study provides a method for the synthesis of organic ligand based ionic bismuth halide hybrids with higher QYs, and enriches X-ray scintillation materials.