ADCdb: the database of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a class of innovative biopharmaceutical drugs, which, via their antibody (mAb) component, deliver and release their potent warhead (a.k.a. payload) at the disease site, thereby simultaneously improving the efficacy of delivered therapy and reducing its off-target toxicity. To design ADCs of promising efficacy, it is crucial to have the critical data of pharma-information and biological activities for each ADC. However, no such database has been constructed yet. In this study, a database named ADCdb focusing on providing ADC information (especially its pharma-information and biological activities) from multiple perspectives was thus developed. Particularly, a total of 6572 ADCs (359 approved by FDA or in clinical trial pipeline, 501 in preclinical test, 819 with in-vivo testing data, 1868 with cell line/target testing data, 3025 without in-vivo/cell line/target testing data) together with their explicit pharma-information was collected and provided. Moreover, a total of 9171 literature-reported activities were discovered, which were identified from diverse clinical trial pipelines, model organisms, patient/cell-derived xenograft models, etc. Due to the significance of ADCs and their relevant data, this new database was expected to attract broad interests from diverse research fields of current biopharmaceutical drug discovery. The ADCdb is now publicly accessible at: https://idrblab.org/adcdb/.

Immune evasion strategy involving propionylation by the KSHV interferon regulatory factor 1 (vIRF1).

Post-translational modifications (PTMs) are essential for host antiviral immune response and viral immune evasion. Among a set of novel acylations, lysine propionylation (Kpr) has been detected in both histone and non-histone proteins. However, whether protein propionylation occurs in any viral proteins and whether such modifications regulate viral immune evasion remain elusive. Here, we show that Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral interferon regulatory factor 1 (vIRF1) can be propionylated in lysine residues, which is required for effective inhibition of IFN-ß production and antiviral signaling. Mechanistically, vIRF1 promotes its own propionylation by blocking SIRT6's interaction with ubiquitin-specific peptidase 10 (USP10) leading to its degradation via a ubiquitin-proteasome pathway. Furthermore, vIRF1 propionylation is required for its function to block IRF3-CBP/p300 recruitment and repress the STING DNA sensing pathway. A SIRT6-specific activator, UBCS039, rescues propionylated vIRF1-mediated repression of IFN-ß signaling. These results reveal a novel mechanism of viral evasion of innate immunity through propionylation of a viral protein. The findings suggest that enzymes involved in viral propionylation could be potential targets for preventing viral infections.

Modulation of SK Channels via Calcium Buffering Tunes Intrinsic Excitability of Parvalbumin Interneurons in Neuropathic Pain: A Computational and Experimental Investigation.

Parvalbumin-expressing interneurons (PVINs) play a crucial role within the dorsal horn of the spinal cord by preventing touch inputs from activating pain circuits. In both male and female mice, nerve injury decreases PVINs' output via mechanisms that are not fully understood. In this study, we show that PVINs from nerve-injured male mice change their firing pattern from tonic to adaptive. To examine the ionic mechanisms responsible for this decreased output, we used a reparametrized Hodgkin-Huxley type model of PVINs, which predicted (1) the firing pattern transition is because of an increased contribution of small conductance calcium-activated potassium (SK) channels, enabled by (2) impairment in intracellular calcium buffering systems. Analyzing the dynamics of the Hodgkin-Huxley type model further demonstrated that a generalized Hopf bifurcation differentiates the two types of state transitions observed in the transient firing of PVINs. Importantly, this predicted mechanism holds true when we embed the PVIN model within the neuronal circuit model of the spinal dorsal horn. To experimentally validate this hypothesized mechanism, we used pharmacological modulators of SK channels and demonstrated that (1) tonic firing PVINs from naive male mice become adaptive when exposed to an SK channel activator, and (2) adapting PVINs from nerve-injured male mice return to tonic firing on SK channel blockade. Our work provides important insights into the cellular mechanism underlying the decreased output of PVINs in the spinal dorsal horn after nerve injury and highlights potential pharmacological targets for new and effective treatment approaches to neuropathic pain.SIGNIFICANCE STATEMENT Parvalbumin-expressing interneurons (PVINs) exert crucial inhibitory control over Aß fiber-mediated nociceptive pathways at the spinal dorsal horn. The loss of their inhibitory tone leads to neuropathic symptoms, such as mechanical allodynia, via mechanisms that are not fully understood. This study identifies the reduced intrinsic excitability of PVINs as a potential cause for their decreased inhibitory output in nerve-injured condition. Combining computational and experimental approaches, we predict a calcium-dependent mechanism that modulates PVINs' electrical activity following nerve injury: a depletion of cytosolic calcium buffer allows for the rapid accumulation of intracellular calcium through the active membranes, which in turn potentiates SK channels and impedes spike generation. Our results therefore pinpoint SK channels as potential therapeutic targets for treating neuropathic symptoms.

Determining Cognitive Workload Using Physiological Measurements: Pupillometry and Heart-Rate Variability.

The adoption of Industry 4.0 technologies in manufacturing systems has accelerated in recent years, with a shift towards understanding operators' well-being and resilience within the context of creating a human-centric manufacturing environment. In addition to measuring physical workload, monitoring operators' cognitive workload is becoming a key element in maintaining a healthy and high-performing working environment in future digitalized manufacturing systems. The current approaches to the measurement of cognitive workload may be inadequate when human operators are faced with a series of new digitalized technologies, where their impact on operators' mental workload and performance needs to be better understood. Therefore, a new method for measuring and determining the cognitive workload is required. Here, we propose a new method for determining cognitive-workload indices in a human-centric environment. The approach provides a method to define and verify the relationships between the factors of task complexity, cognitive workload, operators' level of expertise, and indirectly, the operator performance level in a highly digitalized manufacturing environment. Our strategy is tested in a series of experiments where operators perform assembly tasks on a Wankel Engine block. The physiological signals from heart-rate variability and pupillometry bio-markers of 17 operators were captured and analysed using eye-tracking and electrocardiogram sensors. The experimental results demonstrate statistically significant differences in both cardiac and pupillometry-based cognitive load indices across the four task complexity levels (rest, low, medium, and high). Notably, these developed indices also provide better indications of cognitive load responding to changes in complexity compared to other measures. Additionally, while experts appear to exhibit lower cognitive loads across all complexity levels, further analysis is required to confirm statistically significant differences. In conclusion, the results from both measurement sensors are found to be compatible and in support of the proposed new approach. Our strategy should be useful for designing and optimizing workplace environments based on the cognitive load experienced by operators.

Polyoxometalate Li3 PW12 O40 and Li3 PMo12 O40 Electrolytes for High-energy All-solid-state Lithium Batteries.

Solid-state lithium (Li) batteries promise both high energy density and safety while existing solid-state electrolytes (SSEs) fail to satisfy the rigorous requirements of battery operations. Herein, novel polyoxometalate SSEs, Li3 PW12 O40 and Li3 PMo12 O40 , are synthesized, which exhibit excellent interfacial compatibility with electrodes and chemical stability, overcoming the limitations of conventional SSEs. A high ionic conductivity of 0.89 mS cm-1 and a low activation energy of 0.23 eV are obtained due to the optimized three-dimensional Li+ migration network of Li3 PW12 O40 . Li3 PW12 O40 exhibits a wide window of electrochemical stability that can both accommodate the Li anode and high-voltage cathodes. As a result, all-solid-state Li metal batteries fabricated with Li/Li3 PW12 O40 /LiNi0.5 Co0.2 Mn0.3 O2 display a stable cycling up to 100 cycles with a cutoff voltage of 4.35 V and an areal capacity of more than 4 mAh cm-2 , as well as a cost-competitive SSEs price of $5.68 kg-1 . Moreover, Li3 PMo12 O40 homologous to Li3 PW12 O40 was obtained via isomorphous substitution, which formed a low-resistance interface with Li3 PW12 O40 . Applications of Li3 PW12 O40 and Li3 PMo12 O40 in Li-air batteries further demonstrate that long cycle life (650 cycles) can be achieved. This strategy provides a facile, low-cost strategy to construct efficient and scalable solid polyoxometalate electrolytes for high-energy solid-state Li metal batteries.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

GIPS-Mix for Accurate Identification of Isomeric Components in Glycan Mixtures Using Intelligent Group-Opting Strategy.

Accurate identification of glycan structures is highly desirable as they are intimately linked to their different functions. However, glycan samples generally exist as mixtures with multiple isomeric structures, making assignment of individual glycan components very challenging, even with the aid of multistage mass spectrometry (MSn). Here, we present an approach, GIPS-mix, for assignment of isomeric glycans within a mixture using an intelligent group-opting strategy. Our approach enumerates all possible combinations (groupings) of candidate glycans and opts in the best-matched glycan group(s) based on the similarity between the simulated spectra of each glycan group and the acquired experimental spectra of the mixture. In the case that a single group could not be elected, a tie break is performed by additional MSn scanning using intelligently selected precursors. With 11 standard mixtures and 6 human milk oligosaccharide fractions, we demonstrate the application of GIPS-mix in assignment of individual glycans in mixtures with high accuracy and efficiency.

RGS5 augments astrocyte activation and facilitates neuroinflammation via TNF signaling.

Astrocytes contribute to chronic neuroinflammation in a variety of neurodegenerative diseases, including Parkinson's disease (PD), the most common movement disorder. However, the precise role of astrocytes in neuroinflammation remains incompletely understood. Herein, we show that regulator of G-protein signaling 5 (RGS5) promotes neurodegenerative process through augmenting astrocytic tumor necrosis factor receptor (TNFR) signaling. We found that selective ablation of Rgs5 in astrocytes caused an inhibition in the production of cytokines resulting in mitigated neuroinflammatory response and neuronal survival in animal models of PD, whereas overexpression of Rgs5 had the opposite effects. Mechanistically, RGS5 switched astrocytes from neuroprotective to pro-inflammatory property via binding to the receptor TNFR2. RGS5 also augmented TNFR signaling-mediated pro-inflammatory response by interacting with the receptor TNFR1. Moreover, interrupting RGS5/TNFR interaction by either RGS5 aa 1-108 or small molecular compounds feshurin and butein, suppressed astrocytic cytokine production. We showed that the transcription of astrocytic RGS5 was controlled by transcription factor early B cell factor 1 whose expression was reciprocally influenced by RGS5-modulated TNF signaling. Thus, our study indicates that beyond its traditional role in G-protein coupled receptor signaling, astrocytic RGS5 is a key modulator of TNF signaling circuit with resultant activation of astrocytes thereby contributing to chronic neuroinflammation. Blockade of the astrocytic RGS5/TNFR interaction is a potential therapeutic strategy for neuroinflammation-associated neurodegenerative diseases.

Enzymatic Catalysis in Size and Volume Dual-Confined Space of Integrated Nanochannel-Electrodes Chip for Enhanced Impedance Detection of Salmonella.

Nanochannel-based confinement effect is a fascinating signal transduction strategy for high-performance sensing, but only size confinement is focused on while other confinement effects are unexplored. Here, a highly integrated nanochannel-electrodes chip (INEC) is created and a size/volume-dual-confinement enzyme catalysis model for rapid and sensitive bacteria detection is developed. The INEC, by directly sandwiching a nanochannel chip (60 µm in thickness) in nanoporous gold layers, creates a micro-droplet-based confinement electrochemical cell (CEC). The size confinement of nanochannel promotes the urease catalysis efficiency to generate more ions, while the volume confinement of CEC significantly enriches ions by restricting diffusion. As a result, the INEC-based dual-confinement effects benefit a synergetic enhancement of the catalytic signal. A 11-times ion-strength-based impedance response is obtained within just 1 min when compared to the relevant open system. Combining this novel nanoconfinement effects with nanofiltration of INEC, a separation/signal amplification-integrated sensing strategy is further developed for Salmonella typhimurium detection. The biosensor realizes facile, rapid (<20 min), and specific signal readout with a detection limit of 9 CFU mL-1 in culturing solution, superior to most reports. This work may create a new paradigm for studying nanoconfined processes and contribute a new signal transduction technique for trace analysis application.

Risk of colorectal cancer after appendectomy: A systematic review and meta-analysis.

BACKGROUND AND AIM: Appendectomy is associated with various diseases, but whether it increases the risk of colorectal cancer (CRC) remains uncertain. We conducted a systematic review and meta-analysis aimed at investigating the suggested correlation between appendectomy and CRC. METHODS: Systematic retrieval was performed using the PubMed, Embase, Cochrane library, Web of Science, and ClinicalTrials.gov databases up to May 4, 2022, for studies reported the influence of appendectomy on CRC, colon cancer (CC) or rectal cancer (RC). Odd ratios (ORs) and 95% confidence intervals (CIs) of CRC after appendectomy were pooled using the random effects model. Subgroup analyses were carried on by region, sex, and tumor location. RESULTS: Our search identified 1743 articles, of which 22 studies from three continents published between 1964 and 2022 were eligible for inclusion. Overall, people with appendectomy had a higher risk of CRC (OR = 1.31; 95% CI [1.05, 1.62]). But the risk for Europeans was not significant (OR = 0.94; 95% CI [0.87, 1.02]; I2  = 0%), while for Americans and Asians, appendectomy would increase the risk of CRC (OR = 1.68; 95% CI [1.15, 2.44]; I2  = 65% and OR = 1.46; 95% CI [1.04, 2.05]; I2  = 98%), especially in females and in developing countries. It is worth noting that appendectomy might be a protective factor for CC in European women (OR = 0.87; 95% CI [0.77, 0.98]; I2  = 0%). CONCLUSIONS: Appendectomy may be a risk factor for CRC, with varying degrees in different populations. More high-quality cross-regional studies are needed for better clinical decision making.

Noninvasive predictive models based on lifestyle analysis and risk factors for early-onset colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high-risk factors and screening high-risk populations may help lower early-onset CRC (EO-CRC) incidence. We developed noninvasive predictive models for EO-CRC and investigated its risk factors. METHODS: This retrospective multicenter study collected information on 1756 patients (811 patients with EO-CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO-CRC. Some variables in the model influenced EO-CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs). RESULTS: All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89-3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29-3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO-CRC occurrence. CONCLUSION: We established noninvasive predictive models for EO-CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO-CRC in the Chinese population.

The Effect of Microplastics-Plants on the Bioavailability of Copper and Zinc in the Soil of a Sewage Irrigation Area.

It is essential to understand the occurrence from and plant bioavailability of soil microplastics to heavy metals in soils to assess their environmental fate and risk. The purpose of this study was to evaluate the effect of different microplastic concentrations on the bioavailability of copper and zinc in soil. The relationship between the availability of heavy metals in soil assessed by chemical methods (soil fractionation) and the bioavailability of copper and zinc assessed by biological methods (accumulation in maize and cucumber leaves) in relation to the concentration of microplastics. The results showed that copper and zinc in soil shifted from stable to effective fraction with increasing polystyrene concentrations, which would increase the toxicity and bioavailability of heavy metals. When the concentration of polystyrene microplastics increased, copper and zinc accumulation in plants increased, chlorophyll a and chlorophyll b decreased, and malondialdehyde increased. It is shown that the addition of polystyrene microplastics promoted the toxicity of copper and zinc and inhibited plant growth.

PPI-Miner: A Structure and Sequence Motif Co-Driven Protein-Protein Interaction Mining and Modeling Computational Method.

Protein-protein interactions (PPIs) play important roles in biological processes of life, and predicting PPIs becomes a critical scientific issue of concern. Most PPIs occur through small domains or motifs (fragments), which are challenging and laborious to map by standard biochemical approaches because they generally require the cloning of several truncation mutants. Here, we present a computational method, named as PPI-Miner, to fish potential protein interacting partners utilizing protein motifs as queries. In brief, this work first developed a motif-matching algorithm designed to identify the proteins that contain sequential or structural similar motifs with the given query motif. Being aligned to the query motif, the binding mode of the discovered motif and its receptor protein will be initially determined to be used to build PPI complexes accordingly. Eventually, a PPI complex structure could be built and optimized with a designed automatic protocol. Besides discovering PPIs, PPI-Miner can also be applied to other areas, i.e., the rational design of molecular glues and protein vaccines. In this work, PPI-Miner was employed to mine the potential cereblon (CRBN) substrates from human proteome. As a result, 1,739 candidates were predicted, and 16 of them have been experimentally validated in previous studies. The source code of PPI-Miner can be obtained from the GitHub repository (https://github.com/Wang-Lin-boop/PPI-Miner), the webserver is freely available for users (https://bailab.siais.shanghaitech.edu.cn/services/ppi-miner), and the database of predicted CRBN substrates is accessible at https://bailab.siais.shanghaitech.edu.cn/services/crbn-subslib.

Signal-on fluorescent sensing strategy for Pb2+ detection based on 8-17 DNAzyme-mediated molecular beacon-type catalytic hairpin assembly circuit.

Based on a Pb2+-specific 8-17 DNAzyme-induced catalytic hairpin assembly (CHA), a simple signal-on fluorescence strategy for lead ion detection was established. 8-17 DNAzyme was used as the recognition element of Pb2+, which catalyzed the cleavage of the RNA base embedded in the DNA substrate strand, while releasing part of the substrate strand (S') as CHA initiator. And two hairpin probes (H1 and H2-FQ) were designed according to the sequence of S' for CHA, in which H2-FQ was labeled with the fluorophore FAM and quencher BHQ-1 as fluorescent "molecular switch" based on fluorescence resonance energy transfer (FRET). In the presence of Pb2+, the CHA reaction was triggered to form a large number of H1-H2 complexes, enabling enzyme-free isothermal amplification and a signal-on fluorescence strategy. In the concentration range of 0.5-1000 nM, the fluorescence signal increases with the increase of Pb2+ concentration. The quantitative detection limit of Pb2+ by this method is 0.5 nM, which has better detection performance compared with the FQ-labeled 8-17 DNAzyme method. The established biosensor exhibits good specificity and can be effectively used for the detection of Pb2+ in real samples of river water and grass carp. Through ingenious nucleic acid sequence design, DNAzyme and CHA reactions are integrated to realize the enzyme-free isothermal amplifications and sensitive detection of Pb2+, which holds potential versatility in food supervision and environmental monitoring.

Telitacicept for Recalcitrant Cutaneous Manifestations of Systemic Lupus Erythematosus: A Case Report and Review of the Literature.

Telitacicept is a novel humanized, recombinant transmembrane activator and calcium modulator and cyclophilin ligand interactor and the Fc portion (TACI-Fc) fusion protein, designed to neutralize the activity of both B-cell lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). On March 9, 2021, telitacicept received its first approval in China for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE). Additionally, on April 15, 2020, the U.S. Food and Drug Administration (FDA) granted fast track designation to telitacicept for the treatment of SLE. Clinical studies of telitacicept in several other indications, including IgA nephropathy, multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorders, rheumatoid arthritis and Sjögren's syndrome are underway in China. This is the first case that reports telitacicept successfully treated a SLE patient with refractory cutaneous involvement, which provides a potential therapeutic option for recalcitrant cutaneous manifestations of SLE. Furthermore, we review reported studies of BLyS targeted treatments for mucocutaneous lupus. Telitacicept appears to have activity in refractory cutaneous involvement of SLE and clinical trials are warranted to further assess this potential therapy.

Efficient removal of Sb(â ¤) from water using sulphidated ferrihydrite via tripuhyite (FeSbO4) precipitation and complexation.

Elevated concentrations of antimony (Sb) in the ecological environment have received considerable attention due to the harmful consequence involved. This study synthesized sulphidated ferrihydrite with different S:Fe molar ratios to efficiently remove Sb(V) from water. As the S:Fe molar ratio ranged from 0.00 to 1.48, the removal efficiency of Sb(V) by sulphidated ferrihydrite first decreased before increasing considerably. Sulphidated ferrihydrite with an S:Fe molar ratio of 0.74 exhibited a strong affinity towards Sb(V) with an optimal removal capacity of 963.74 mg Sb/g, which was 3.2-fold higher than that of ferrihydrite. In the kinetic experiments, the removal behavior of Sb(V) was well described by the pseudo-second-order model, suggesting that the removal process was controlled via chemisorption. Moreover, Sb(V) was efficiently removed over a wide pH range of 3.00-11.00, and coexisting anions (NO3-, Cl-, SO42-, SiO32-, CO32- and PO43-) exhibited marginal impact on the Sb(V) removal by sulphidated ferrihydrite (S:Fe ≥ 0.44). The characterization results of XRD, SEM, TEM mapping and etched XPS revealed goethite to be the dominant phase of sulphidated ferrihydrite with an S:Fe molar ratio of 0.15, while a mixed constitution of mixed-valent iron (hydro)oxides and iron sulphide was formed when the S:Fe molar ratio exceeded 0.44. Moreover, sulphidated ferrihydrite acted as a donor for Fe and S for the effective retention of Sb(V) by two main pathways: precipitation (tripuhyite, FeSbO4) and complexation (≡S-H and ≡Fe-OH). Therefore, sulphidated ferrihydrite is a promising material for eliminating Sb(V) contamination from water.

Examining the relationships between medical students' preferred online instructional strategies, course difficulty level, learning performance, and effectiveness.

Students' preferences and engagement with online educational resources and activities are crucial for academic success in the context of online medical education. This study investigated the preferences of Chinese medical students regarding the teaching strategies used by instructors and their relationship with course difficulty level, student's academic performance, and perceived effectiveness. Survey data (n = 375) were collected from the medical students from one of the largest medical schools in Southern China during the spring semester of 2020. First, exploratory factor analysis demonstrated that there were three latent factors behind online teaching strategies, including teacher-led instructional strategies, supervised and monitored learning strategies, and self-directed learning strategies. Instructional activities under teacher supervision and monitoring received the highest rating while teacher-led strategies received the lowest ratings. Second, the popularity of the three online instructional strategies we have identified was positively associated with students' perceived effectiveness of online teaching and their self-reported academic performance. Third, analysis of the quantified answers to the open-ended question reported a positive association between the perceived difficulty level of the courses and students' preference of teacher-led strategies. It also manifested a positive correlation between perceived effectiveness level of the online teaching and the use of self-directed learning strategies before their online lectures. Further implications of the findings are fully discussed.

Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics.

Fabrication of a multifunctional near-infrared (NIR) theranostic nanoplatform has attracted increasing attention. Indocyanine green (ICG), a clinic-approved NIR fluorescence-imaging agent, is an excellent photothermal agent candidate. However, the stability and tumor targeting are still great obstacles for its wide application. In this work, C-phycocyanin (CPC) as a tumor-associated macrophages (TAMs) targeted vehicle was used to fabricate noncovalent ICG conjugate of CPC (ICG@CPC) via self-assembly in aqueous media. Compared to free ICG, ICG@CPC displays improved stabilities in aqueous solutions and under light irradiation and threefold increase in photothermal conversion efficiency. The in vitro results indicated that ICG@CPC could be selectively internalized into J774A.1 cells via SR-A-mediated endocytosis and lead to enhanced photocytotoxicity against J774A.1 cells. In vivo results showed that ICG@CPC had significantly improved drug accumulation in the tumor and photothermal therapeutic efficacy relative to ICG alone. This study for the first time utilizes CPC as a TAMs-targeted nanocarrier for ICG and may promote further rational design of ICG-based photothermal nanodrugs for precise and efficient cancer theranosis.

Occurrence and genomic characterization of ESBL-producing Escherichia coli ST29 strains from swine with abundant virulence genes.

Food-production animals were considered to be a major reservoir of antimicrobial-resistant bacteria and clinically relevant pathogens. The potential of commensal Escherichia coli from pigs as a source of opportunistic pathogens associated with extraintestinal infections in humans needs to be assessed. In this study, 13 E. coli isolates from an intensive pig farm in China were analyzed using whole genome sequencing followed by in-depth in silico analysis. Genomic analysis showed comprehensive antimicrobial resistance profiles, with each isolate carrying between 4 and 22 antimicrobial resistance genes. Although these E. coli isolates were assigned to low-virulence phylogroup A and B1, 31 different virulence genes were detected at least once in the 13 sequenced isolates. Extraintestinal pathogenic E. coli-associated virulence genes, including iss, iha, tsh and iroN, were found in commensal E. coli isolates in this study. Of note, a large number of virulence genes (n = 22) were identified in ESBL-producing E. coli sequence type (ST) 29 isolates. Our study revealed the presence of comprehensive antimicrobial resistance and virulence gene profiles in commensal E. coli isolates of pigs. The emerged ESBL-producing E. coli ST 29 isolates harboring a high abundance of VAGs highlighted that this new clonal linage may pose a threat to public health.

Multinuclear Transition Metal Sandwich-Type Polytungstate Derivatives for Enhanced Electrochemical Energy Storage and Bifunctional Electrocatalysis Performances.

Different transition metal (TM) units are introduced into a trivacant Keggin cluster to form three sandwich polytungstate derivatives, (H2en)[{K(H2O)0.5}2{K2(H2O)3}{Ni(H2O)(en)2}2{Ni4(H2O)2(PW9O34)2}] (1), [Cu6(Himi)6{AsIIIW9O33}2]·5H2O (2), and (H2btp)4[FeIII2FeII2(H2O)2(AsW9 O34)2]·4H2O (3) (en = ethanediamine; imi = imidazole; btp = 1,3-bis(1, 2, 4-triazol-1-yl) propane). Compound 1 is a 2,3,8-connected 3D network with {43}2{46·66·83·612·8}{6}2 topology based on bisupported tetra-Ni sandwich phosphotungstate and two kinds of potassium connection units. Compound 2 is a dense 12-connected 3D supramolecular network with {324·436·56} topology based on hexa-Cu(imi) sandwiched arsenotungstate. Compound 3 represents the first mixed valence tetra-Fe substituted sandwich arsenotungstate assembly. Compounds 1-3 show enhanced supercapacitor performance (618.2, 603.4, and 504.6 F·g-1 at a current density of 2.4 A·g-1 with 91.5%, 89.3%, and 87.8% of cycle efficiency after 5000 cycles, respectively) compared to their maternal polyoxometalates (POMs) and most reported POM-based electrode materials, which suggests that the introduction of multinuclear TM into vacant POMs is an effective method to improve the energy storage performance of POMs. In addition, compounds 1 and 3 exhibit dual-functional electrocatalytic behaviors in the reduction of iodate and the oxidation of dopamine for introduction of {Ni4} and {Fe4} units.