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Traditional Chinese Medicine (TCM) is a supremely valuable resource for the development of drug discovery. Few methods are capable of hunting for potential molecule ligands from TCM towards more than one single protein target. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed to perform targeted compound screening of two key proteins involved in the cellular invasion process of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): the spike (S) protein receptor binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2)...

Recently, we have developed novel Pim-1 kinase inhibitors starting from a dihydrobenzofuran core structure using a computational approach. Here, we report the design and synthesis of stilbene-based Pim-1 kinase inhibitors obtained by formal elimination of the dihydrofuran ring. These inhibitors of the first design cycle, which were obtained as inseparable cis/trans mixtures, showed affinities in the low single-digit micromolar range. To be able to further optimize these compounds in a structure-based fashion, we determined the X-ray structures of the protein-ligand-complexes...

Tuning electronic characteristics of metal-ligand bonds based on reaction pathways to achieve efficient catalytic processes has been widely studied and proven to be feasible in homogeneous catalysis, but it is scarcely investigated in heterogeneous catalysis. Herein, we demonstrate the regulation of the electronic configuration of Ir-O bonds in an Ir single-atom catalyst according to the borane activation mechanism. Ir-O bonds in Ir1 /Ni(OH) x are found to be more electron-poor than those in Ir1 /NiO x . Despite the mild solvent-free conditions and ambient temperature, Ir1 /Ni(OH) x exhibits outstanding performance for the hydroboration of alkenes, furnishing the desired alkylboronic esters with a turnover frequency value of ≤3060 h-1 and 99% anti-Markovnikov selectivity, which is significantly better than that of Ir1 /NiO x (42 h-1 )...

BACKGROUND AND OBJECTIVES: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive. METHODS: Combining magnetic resonance (MR) spectroscopy and [11 C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD...

BACKGROUND AND OBJECTIVES: Intramuscular fat fraction (FF) assessed using quantitative MRI (qMRI) has emerged as one of the few responsive outcome measures in CMT1A suitable for future clinical trials. This study aimed to identify the relevance of multiple qMRI biomarkers for tracking longitudinal changes in CMT1A and to assess correlations between MRI metrics and clinical parameters. METHODS: qMRI was performed in CMT1A patients at 2 time points, a year apart, and various metrics were extracted from 3-dimensional volumes of interest at thigh and leg levels...

BACKGROUND AND OBJECTIVES: Structural imaging can offer insights into the cortical morphometry of migraine, which might reflect adaptations to recurring nociceptive messaging. This study compares cortical morphometry between a large sample of people with migraine and healthy controls, as well as across migraine subtypes. METHODS: Adult participants with migraine and age-matched and sex-matched healthy controls attended a single MRI session with magnetization-prepared rapid acquisition gradient echo and fluid-attenuated inversion recovery sequences at 3T...

PURPOSE: Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. METHODS: In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT...

OBJECTIVE: Body mass index (BMI) is known to contribute to outcomes for patients with knee OA. Furthermore, BMI influences the protein expression of orthobiologic treatments like platelet-rich plasma (PRP) and microfragmented adipose tissue (MFAT). We performed a secondary analysis of the association of BMI with PROs for patients with knee OA who received either PRP or MFAT injections. METHODS: Seventy-one patients with knee OA were randomized to receive a single ultrasound-guided injection of PRP or MFAT...

BACKGROUND: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM. METHODS: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases...

BACKGROUND AND PURPOSE: Soft tissue defects after total knee arthroplasties (TKA) represent a major orthopedic challenge with amputation as a feared outcome. Microvascular free flap coverage (FFC) can increase limb salvage rates, but complications related to the procedure are yet to be explored further. We aimed to review a single-center experience with FFC for soft tissue defects related to revision total knee arthroplasty. METHODS: Through a retrospective chart review from 2006 to 2021, we identified all patients who had FFC of a knee with an existing TKA...

AIMS: Photoplethysmography- (PPG) based smartphone applications facilitate heart rate and rhythm monitoring in patients with paroxysmal and persistent atrial fibrillation (AF). Despite an endorsement from the European Heart Rhythm Association, validation studies in this setting are lacking. Therefore, we evaluated the accuracy of PPG-derived heart rate and rhythm classification in subjects with an established diagnosis of AF in unsupervised real-world conditions. METHODS AND RESULTS: Fifty consecutive patients were enrolled, 4 weeks before undergoing AF ablation...

GOALS: We aimed to evaluate whether direct access colonoscopy (DAC) is noninferior to office-scheduled colonoscopy (OSC) for achieving successful colonoscopy. BACKGROUND: DAC may improve access to colonoscopy. We developed an algorithm assessing eligibility, risk for inadequate preparation, and need for nursing/navigator assistance. STUDY: This was a retrospective, single-center study of DAC and OSC patients from June 5, 2018, to July 31, 2019...

BACKGROUND: Typhoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia. METHODS: Consecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015-2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S...

Filariasis, a neglected tropical disease caused by roundworms, is a significant public health concern in many tropical countries. Microscopic examination of blood samples can detect and differentiate parasite species, but it is time consuming and requires expert microscopists, a resource that is not always available. In this context, artificial intelligence (AI) can assist in the diagnosis of this disease by automatically detecting and differentiating microfilariae. In line with the target product profile for lymphatic filariasis as defined by the World Health Organization, we developed an edge AI system running on a smartphone whose camera is aligned with the ocular of an optical microscope that detects and differentiates filarias species in real time without the internet connection...

Ceramic materials with high strength and chemical inertness are widely used as engineering materials. However, the brittle nature limits their applications as fracture occurs before the onset of plastic yielding. There has been limited success despite extensive efforts to enhance the deformability of ceramics. Here we report a method for enhancing the room temperature plastic deformability of ceramics by artificially introducing abundant defects into the materials via preloading at elevated temperatures. After the preloading treatment, single crystal (SC) TiO2 exhibited a substantial increase in deformability, achieving 10% strain at room temperature...

Caves and lava tubes on the Moon and Mars are sites of geological and astrobiological interest but consist of terrain that is inaccessible with traditional robot locomotion. To support the exploration of these sites, we present ReachBot, a robot that uses extendable booms as appendages to manipulate itself with respect to irregular rock surfaces. The booms terminate in grippers equipped with microspines and provide ReachBot with a large workspace, allowing it to achieve force closure in enclosed spaces, such as the walls of a lava tube...

BACKGROUND: Vaccination is one of the most cost-effective public health interventions used to prevent diseases in susceptible populations. Despite the established efficacy of vaccines, there are many reasons people are hesitant about vaccination, and these reasons could be complex. This rapid survey estimated the prevalence of COVID-19 vaccine hesitancy and potentially contributing factors in Montserrado and Nimba counties in Liberia. METHODS: A cross-sectional study was conducted among adults living in Liberia...

It is significant to systematically quantify the propagation thresholds of meteorological drought to different levels of agricultural drought in karst areas, and revealit's the propagation driving mechanisms. This can guide early warning and fine management of agricultural drought. In this study,we selected Guizhou Province as an example. The standardized precipitation evapotranspiration index (SPEI) and standardized soil moisture index (SSI) were used to characterize meteorological and agricultural drought...

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls...

The purpose of this study was to examine transient plasma membrane disruptions (TPMDs) and TPMD-induced Ca++ waves (TPMD Ca++ Wvs) in human and mouse corneal epithelium (HCEC and MCEC). A multi-photon microscope was used to create laser-induced TPMDs in single cultured cells and in intact ex vivo and in vivo MCECs and ex vivo human cornea rim HCECs. Eye rubbing-induced TPMDs were studied by gentle rubbing with a cotton tipped applicator over a closed eyelid in ex vivo and in vivo MCECs. Ca++ sources for TPMD-induced Ca++ waves were explored using Ca++ channel inhibitors and Ca++-free media...