Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial.

Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0-15.0] vs. 15.0 days [14.0-15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies. Funding: Fujian Akeylink Biotechnology Co., Ltd.

Compound Similarity Network as a Novel Data Mining Strategy for High-Throughput Investigation of Degradation Pathways of Organic Pollutants in Industrial Wastewater Treatment.

Identification of degradation products and pathways is crucial for investigating emerging pollutants and evaluation of wastewater treatment methods. Nontargeted analysis is a powerful tool to comprehensively investigate the degradation pathways of organic pollutants in real-world wastewater samples but often generates large data sets, making it difficult to effectively locate the exact information on interests. Herein, to efficiently establish the linkages among compounds in the same degradation pathways, we introduce a compound similarity network (CSN) as a novel data mining strategy for LC-MS-based nontargeted analysis of complex wastewater samples. Different from molecular networks that cluster compounds based on MS/MS spectra similarity, our CSN strategy harnesses molecular fingerprints to establish linkages among compounds and thus is spectra-independent. The effectiveness of CSN was demonstrated by nontargeted identification of degradation pathways and products of organic pollutants in leather industrial wastewater that underwent laboratory-scale activated carbon adsorption (ACD) and ozonation treatments. Utilizing CSN in interpreting nontargeted data, we tentatively annotated 4324 compounds in the untreated leather industrial wastewater, 3246 after ACD, and 3777 after ACD/ozonation. We located 145 potential degradation pathways of organic pollutants in the ACD/ozonation process using CSN and validated 7 pathways with 15 chemical standards. CSN also revealed 5 clusters of emerging pollutants, from which 3 compounds were selected for in vitro cytotoxicity study to evaluate their potential biohazards as new pollutants. As CSN offers an efficient way to connect massive compounds and to find multiple degradation pathways in a high-throughput manner, we anticipate that it will find wide applications in nontargeted analysis of diverse environmental samples.

Exploration of the biodegradation pathway and enhanced removal of imazethapyr from soil by immobilized Bacillus marcorestinctum YN1.

Excessive or inappropriate applications of imazethapyr cause severe ecological deteriorations and health risks in human. A novel bacterial strain, i.e., Bacillus marcorestinctum YN1, was isolated to efficiently degrade imazethapyr, with the degradation pathways and intermediates predicted. Protein mass spectrometry analysis identified enzymes in strain YN1 potentially involved in imazethapyr biodegradation, including methylenetetrahydrofolate dehydrogenase, carbon-nitrogen family hydrolase, heme degrading monooxygenase, and cytochrome P450. The strain YN1 was further immobilized with biochar (BC600) prepared from mushroom waste (i.e., spent mushroom substrate) by pyrolysis at 600 °C to evaluate its degrading characteristics of imazethapyr. Scanning electron microscope observation showed that strain YN1 was adsorbed in the rich pore structure of BC600 and the adsorption efficiency reached the maximum level of 88.02% in 6 h. Both energy dispersive X-ray and Fourier transform infrared spectroscopy analyses showed that BC600 contained many elements and functional groups. The results of liquid chromatography showed that biochar-immobilized strain YN1 (IBC-YN1) improved the degradation rate of imazethapyr from 79.2% to 87.4%. The degradation rate of imazethapyr by IBC-YN1 could still reach 81.0% in the third recycle, while the bacterial survival rate was 67.73% after 180 d storage at 4 °C. The treatment of IBC-YN1 significantly shortened the half-life of imazethapyr in non-sterilized soil from 35.51 to 11.36 d, and the vegetative growth of imazethapyr sensitive crop plant (i.e., Cucumis sativus L.) was significantly increased in soil remediated, showing that the inhibition rate of root length and fresh weight were decreased by 12.45% and 38.49% respectively. This study exhanced our understanding of microbial catabolism of imazethapyr, and provided a potential in situ remediation strategy for improving the soil environment polluted by imazethapyr.

Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171.

This study is aimed to evaluate the safety, tolerability, and pharmacokinetics (PK), as well as to select an appropriate dosing regimen for the pivotal clinical trial of GST-HG171, an orally bioavailable, potent, and selective 3CL protease inhibitor by a randomized, double-blind, and placebo-controlled phase I trial in healthy subjects. We conducted a Ph1 study involving 78 healthy subjects to assess the safety, tolerability, and PK of single ascending doses (150-900 mg) as well as multiple ascending doses (MADs) (150 and 300 mg) of GST-HG171. Additionally, we examined the food effect and drug-drug interaction of GST-HG171 in combination with ritonavir through a MAD regimen of GST-HG171/ritonavir (BID or TID) for 5 days. Throughout the course of these studies, no serious AEs or deaths occurred, and no AEs necessitated study discontinuation. We observed that food had no significant impact on the exposure of GST-HG171. However, the presence of ritonavir substantially increased the exposure of GST-HG171, which facilitated the selection of the GST-HG171/ritonavir dose and regimen (150/100 mg BID) for subsequent phase II/III trials. The selected dose regimen was achieved through concentrations continuously at 6.2-9.9-fold above the levels required for protein-binding adjusted 50% inhibition (IC50) of viral replication in vitro. The combination of 150 mg GST-HG171/100 mg ritonavir demonstrated favorable safety and tolerability profiles. The PK data obtained from GST-HG171/ritonavir administration guided the selection of appropriate dose for a pivotal phase II/III trial currently in progress. (This study has been registered at ClinicalTrials.gov under identifier NCT05668897).

Smart city construction and green technology innovation: evidence at China's city level.

In the context of China's economic and social transformation, smart cities are becoming increasingly important for green development. Based on pilot smart cities and panel data from 274 prefecture-level cities in China from 2006 to 2018, this paper mainly evaluates the impact of smart city construction (SCC) on green technology innovation (GTI). To analyze SCC mechanisms and heterogeneity, we used China's smart city pilots as a quasi-natural experiment. In terms of the influencing mechanism, SCC can promote GTI by enhancing the digital economy level. Meanwhile, the optimization allocation of resources, including labor, land, and capital, can effectively foster the promoting effect of SCC on GTI. Moreover, SCC has a spatial diffusion effect; it will not only promote local GTI, but also improve the level of GTI in neighboring cities. In terms of the heterogeneity analysis, smart cities, which present a large scales, rich human capital, and high-level infrastructure, have a strongly positive effect on GTI. This study provides important empirical evidence for the development of SCC and GTI.

Tunable electronic and optical properties of ferroelectric WS2/Ga2O3heterostructures.

To integrate two-dimensional (2D) materials into van der Waals heterostructures (vdWHs) is regarded as an effective strategy to achieve multifunctional devices. The vdWHs with strong intrinsic ferroelectricity is promising for applications in the design of new electronic devices. The polarization reversal transitions of 2D ferroelectric Ga2O3layers provide a new approach to explore the electronic structure and optical properties of modulated WS2/Ga2O3vdWHs. The WS2/Ga2O3↑ and WS2/Ga2O3↓ vdWHs are designed to explore possible characteristics through the electric field and biaxial strain. The biaxial strain can effectively modulate the mutual transition of two mode vdWHs in type II and type I band alignment. The strain engineering enhances the optical absorption properties of vdWHs, encompassing excellent optical absorption properties in the range from infrared to visible to ultraviolet, ensuring promising applications in flexible electronics and optical devices. Based on the highly modifiable physical properties of the WS2/Ga2O3vdWHs, we have further explored the potential applications for the field-controlled switching of the channel in MOSFET devices.

Recent progress on rapid diagnosis of COVID-19 by point-of-care testing platforms.

The outbreak of COVID-19 has drawn great attention around the world. SARS-CoV-2 is a highly infectious virus with occult transmission by many mutations and a long incubation period. In particular, the emergence of asymptomatic infections has made the epidemic even more severe. Therefore, early diagnosis and timely management of suspected cases are essential measures to control the spread of the virus. Developing simple, portable, and accurate diagnostic techniques for SARS-CoV-2 is the key to epidemic prevention. The advantages of point-of-care testing technology make it play an increasingly important role in viral detection and screening. This review summarizes the point-of-care testing platforms developed by nucleic acid detection, immunological detection, and nanomaterial-based biosensors detection. Furthermore, this paper provides a prospect for designing future highly accurate, cheap, and convenient SARS-CoV-2 diagnostic technology.

Enabling a universal lateral flow readout for DNA strand displacement via disassembling chemical labels.

Herein, we describe a novel strategy that enables lateral flow readout for DNA strand displacement via disassembling chemical labels (DCL). Comparing it to a classic fluorogenic assay, we demonstrate that our DCL-based lateral flow assay is highly sensitive and specific, capable of discriminating single nucleotide variants in buccal swab samples.

Reconfigurable band alignment of SWSe/h-BP heterostructures for photoelectric applications.

The integration of two-dimensional (2D) materials into van der Waals heterostructures (vdWHs) is regarded as an effective strategy for fabricating multifunctional devices. Herein, the effects of the vertical electric field and biaxial strain on the electronic, optical and transport properties of SeWS (SWSe)/h-BP vdWHs are systematically investigated using density functional theory calculations. The study shows that electric fields and biaxial strain can modulate not only the band gap but also the band alignment to produce multifunctional device applications. The SWSe/h-BP vdWHs can be used as highly efficient 2D exciton solar cells with a power conversion efficiency of up to 20.68%. In addition, the SWSe/h-BP vdWHs present a significant negative differential resistance (NDR) with a peak-to-valley ratio of 1.12 (1.18). The present work may provide a direction for tunable multiple-band alignments in SWSe/h-BP vdWHs and help achieve multifunctional device applications.

Photo-Enhanced Chemo-Transistor Platform for Ultrasensitive Assay of Small Molecules.

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.

Single-Atom Anchored g-C3N4 Monolayer as Efficient Catalysts for Nitrogen Reduction Reaction.

Electrochemical N2 reduction reaction (NRR) is a promising approach for NH3 production under mild conditions. Herein, the catalytic performance of 3d transition metal (TM) atoms anchored on s-triazine-based g-C3N4 (TM@g-C3N4) in NRR is systematically investigated by density functional theory (DFT) calculations. Among these TM@g-C3N4 systems, the V@g-C3N4, Cr@g-C3N4, Mn@g-C3N4, Fe@g-C3N4, and Co@g-C3N4 monolayers have lower ΔG(*NNH) values, especially the V@g-C3N4 monolayer has the lowest limiting potential of -0.60 V and the corresponding limiting-potential steps are *N2+H++e-=*NNH for both alternating and distal mechanisms. For V@g-C3N4, the transferred charge and spin moment contributed by the anchored V atom activate N2 molecule. The metal conductivity of V@g-C3N4 provides an effective guarantee for charge transfer between adsorbates and V atom during N2 reduction reaction. After N2 adsorption, the p-d orbital hybridization of *N2 and V atoms can provide or receive electrons for the intermediate products, which makes the reduction process follow acceptance-donation mechanism. The results provide an important reference to design high efficiency single atom catalysts (SACs) for N2 reduction.

Predicting and Analyzing Restenosis Risk after Endovascular Treatment in Lower Extremity Arterial Disease: Development and Assessment of a Predictive Nomogram.

PURPOSE: This study aimed to develop and internally validate nomograms for predicting restenosis after endovascular treatment of lower extremity arterial diseases. MATERIALS AND METHODS: A total of 181 hospitalized patients with lower extremity arterial disease diagnosed for the first time between 2018 and 2019 were retrospectively collected. Patients were randomly divided into a primary cohort (n=127) and a validation cohort (n=54) at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression was used to optimize the feature selection of the prediction model. Combined with the best characteristics of LASSO regression, the prediction model was established by multivariate Cox regression analysis. The predictive models' identification, calibration, and clinical practicability were evaluated by the C index, calibration curve, and decision curve. The prognosis of patients with different grades was compared by survival analysis. Internal validation of the model used data from the validation cohort. RESULTS: The predictive factors included in the nomogram were lesion site, use of antiplatelet drugs, application of drug coating technology, calibration, coronary heart disease, and international normalized ratio (INR). The prediction model demonstrated good calibration ability, and the C index was 0.762 (95% confidence interval: 0.691-0.823). The C index of the validation cohort was 0.864 (95% confidence interval: 0.801-0.927), which also showed good calibration ability. The decision curve shows that when the threshold probability of the prediction model is more significant than 2.5%, the patients benefit significantly from our prediction model, and the maximum net benefit rate is 30.9%. Patients were graded according to the nomogram. Survival analysis found that there was a significant difference in the postoperative primary patency rate between patients of different classifications (log-rank p<0.001) in both the primary cohort and the validation cohort. CONCLUSION: We developed a nomogram to predict the risk of target vessel restenosis after endovascular treatment by considering information on lesion site, postoperative antiplatelet drugs, calcification, coronary heart disease, drug coating technology, and INR. CLINICAL IMPACT: Clinicians can grade patients after endovascular procedure according to the scores of the nomograms and apply intervention measures of different intensities for people at different risk levels. During the follow-up process, an individualized follow-up plan can be further formulated according to the risk classification. Identifying and analyzing risk factors is essential for making appropriate clinical decisions to prevent restenosis.

Janus biomass aerogel for Highly-Efficient steam Generation, Desalination, degradation of organics and water disinfection.

Solar-driven water purification has been deemed as a cheap, green and renewable technology to mitigate water shortage and pollution. Herein, a biomass aerogel with hydrophilic-hydrophobic Janus structure has been prepared as solar water evaporator, which is achieved by partially modifying hydrothermal-treated loofah sponge (HLS) with reduced graphene oxide (rGO). It's a rare design philosophy that HLS serves as a substrate with large pores and hydrophilic properties to ensure continuous and effective water transport, and the hydrophobic layer with rGO modification guarantees good salt resistance in seawater desalination with high photothermal conversion efficiency. As a result, the obtained Janus aerogel, p-HLS@rGO-12, exhibits impressive solar-driven evaporation rates of 1.75 kg m-2h-1 and 1.54 kg m-2h-1 for pure water and seawater respectively, with good cycling stability in the evaporation process. Furthermore, p-HLS@rGO-12 also demonstrates outstanding photothermal degradation of rhodamine B (greater than98.8 % in 2 h) and sterilization of E. coli (nearly 100 % in 2 h). This work offers an unusual approach to achieve highly efficient solar-driven steam generation, seawater desalination, organic pollutant degradation, and water disinfection simultaneously. The prepared Janus biomass aerogel holds great potential application in the field of seawater desalination and wastewater purification.

Immobilization of bacterial mixture of Klebsiella variicola FH-1 and Arthrobacter sp. NJ-1 enhances the bioremediation of atrazine-polluted soil environments.

In this study, the effects of the immobilized bacterial mixture (IM-FN) of Arthrobacter sp. NJ-1 and Klebsiella variicola strain FH-1 using sodium alginate-CaCl2 on the degradation of atrazine were investigated. The results showed that the optimal ratio of three types of carrier materials (i.e., rice straw powder, rice husk, and wheat bran) was 1:1:1 with the highest adsorption capacity for atrazine (i.e., 3774.47 mg/kg) obtained at 30°C. On day 9, the degradation efficiency of atrazine (50 mg/L) reached 98.23% with cell concentration of 1.6 × 108 cfu/ml at pH 9 and 30°C. The Box-Behnken method was used to further optimize the culture conditions for the degradation of atrazine by the immobilized bacterial mixture. The IM-FN could be reused for 2-3 times with the degradation efficiency of atrazine maintained at 73.0% after being stored for 80 days at 25°C. The population dynamics of IM-FN was explored with the total soil DNA samples specifically analyzed by real-time PCR. In 7 days, the copy numbers of both PydC and estD genes in the IM-FN were significantly higher than those of bacterial suspensions in the soil. Compared with bacterial suspensions, the IM-FN significantly accelerated the degradation of atrazine (20 mg/kg) in soil with the half-life shortened from 19.80 to 7.96 days. The plant heights of two atrazine-sensitive crops (wheat and soybean) were increased by 14.99 and 64.74%, respectively, in the soil restored by immobilized bacterial mixture, indicating that the IM-FN significantly reduced the phytotoxicity of atrazine on the plants. Our study evidently demonstrated that the IM-FN could significantly increase the degradation of atrazine, providing a potentially effective bioremediation technique for the treatment of atrazine-polluted soil environment and providing experimental support for the wide application of immobilized microorganism technology in agriculture.

Theoretical exploration of the structural, electronic and optical properties of g-C3N4/C3N heterostructures.

Integration of graphene-like carbon nitride materials is essential for nanoelectronic applications. Using density-functional theory (DFT), we systematically investigate the structural, electronic and optical properties of a s-triazine-based g-C3N4/C3N heterostructure under different modified conditions. The g-C3N4/C3N van der Waals heterostructure (vdWH) formed has an indirect bandgap with type-II band alignment and the band structures can be tuned from type-II band alignment to type-I band alignment by applying biaxial strains and external electric fields (Efield). Compared to single transition metal (TM) atoms at g-C3N4/C3N surfaces, the TM atoms anchored in the interlayer region exhibit more stability, and the corresponding bandgaps are changed from 0.19 eV to 0.61 eV. In addition, the g-C3N4/C3N heterostructure has a strong absorption coefficient in the ultraviolet-visible light region along the x direction. It is found that compressive strain has a large influence on the absorption coefficient of the g-C3N4/C3N system. With the increased compressive strain, the absorption spectra in the visible light region disappeared. Tensile strain has a slight effect on the absorption range, but causes a red shift of the absorption spectrum. In comparison, the light absorption coefficient of the g-C3N4/C3N system remains almost unchanged under the Efield conditions. In summary, the formation of a s-triazine-based g-C3N4/C3N heterostructure has shown potential for applications in nanoelectronic and optoelectronic devices.

Bioinspired MoS2 Nanosheet-Modified Carbon Fibers for Synergetic Bacterial Elimination and Wound Disinfection.

Bacterial infection is one of the most frequent wound complications and has become a major public health concern. Increasing resistance to antibiotics has been noted with these agents broadly used in wound management. It is an urgent demand to develop alternative antibacterial strategies with a reduced chance of resistance. Herein, a Nepenthes-mimicking nanosheet array of MoS2 on carbon fibers (CF-MoS2 ) is proposed to achieve dual bactericidal activities. First, the sharp edges of synthesized surfaces are capable of inducing physical disruption of cell membranes, demonstrating mechanical antibacterial activity like their natural counterparts. Second, in the presence of near-infrared light, bioinspired CF-MoS2 nanosheets are able to cause the death of damaged bacteria owing to their inherent photothermal properties. Such dual-functional modes endow the surfaces with nearly 100% killing efficiency for highly concentrated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, their potential to be applied as wound dressings for photothermal treatment of infectious wounds is also investigated in vivo. Bioinspired CF-MoS2 dressings show advantages of synergistic disinfection and efficient promotion of wound regeneration. It is foreseen that this high-performance and multifunctional CF-MoS2 could afford a feasible broad-spectrum treatment for non-antibiotic disinfection.

Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model.

BACKGROUND: Patients with critical limb ischemia (CLI) are at great risk of major amputation and cardiovascular events. Adipose-derived mesenchymal stem cell (ADSC) therapy is a promising therapeutic strategy for CLI, but the poor engraftment and insufficient angiogenic ability of ADSCs limit their regenerative potential. Herein, we explored the potential of human umbilical vein endothelial cells (HUVECs)-derived small extracellular vesicles (sEVs) for enhancing the therapeutic efficacy of ADSCs in CLI. RESULTS: sEVs derived from hypoxic HUVECs enhanced the resistance of ADSCs to reactive oxygen species (ROS) and further improved the proangiogenic ability of ADSCs in vitro. We found that the hypoxic environment altered the composition of sEVs from HUVECs and that hypoxia increased the level of miR-486-5p in sEVs. Compared to normoxic sEVs (nsEVs), hypoxic sEVs (hsEVs) of HUVECs significantly downregulated the phosphatase and tensin homolog (PTEN) via direct targeting of miR-486-5p, therefore activating the AKT/MTOR/HIF-1α pathway and influencing the survival and pro-angiogenesis ability of ADSCs. In a hindlimb ischemia model, we discovered that hsEVs-primed ADSCs exhibited superior cell engraftment, and resulted in better angiogenesis and tissue repair. CONCLUSION: hsEVs could be used as a therapeutic booster to improve the curative potential of ADSCs in a limb ischemia model. This finding offers new insight for CLI treatment.

Capture and detection of Escherichia coli with graphene aerogels.

Some pathogenic bacteria may cause serious food poisoning as well as catastrophic infections. Thus, it is critical to identify bacteria using simple, quick, and sensitive methods. Herein, we fabricate a graphene aerogel-based biosensing system to capture and detect Escherichia coli (E. coli) with high specificity and sensitivity. A graphene aerogel is prepared by a one-step hydrothermal synthesis method without any reducing reagent. With the help of E. coli antibodies and the graphene foam with a porous structure, E. coli can be captured using the detection substrate with high specificity and selectivity. The electrical resistance and electrochemical impedance spectroscopy (EIS) results of the graphene aerogel foam changed with high sensitivity during E. coli adhesion. Moreover, the resistance change of the graphene device can still be observed when the E. coli concentration was as low as 10 cfu mL-1, while there is no obvious resistance change in the use of Staphylococcus aureus. The subsequent EIS test also found that the charge transfer resistance (Rct) of the detection substrate gradually increased during the E. coli capture process. This nanoelectronic biosensor is simple, quick, safe, and very sensitive, and it may be used as a high-throughput platform for pathogenic bacterial detection, bacterial research, and antimicrobial drug screening.

A CRISPR-based ultrasensitive assay detects attomolar concentrations of SARS-CoV-2 antibodies in clinical samples.

CRISPR diagnostics are powerful tools for detecting nucleic acids but are generally not deployable for the detection of clinically important proteins. Here, we report an ultrasensitive CRISPR-based antibody detection (UCAD) assay that translates the detection of anti-SARS-CoV-2 antibodies into CRISPR-based nucleic acid detection in a homogeneous solution and is 10,000 times more sensitive than the classic immunoassays. Clinical validation using serum samples collected from the general population (n = 197), demonstrates that UCAD has 100% sensitivity and 98.5% specificity. With ultrahigh sensitivity, UCAD enables the quantitative analysis of serum anti-SARS-CoV-2 levels in vaccinated kidney transplant recipients who are shown to produce "undetectable" anti-SARS-CoV-2 using standard immunoassay. Because of the high sensitivity and simplicity, we anticipate that, upon further clinical validation against large cohorts of clinical samples, UCAD will find wide applications for clinical uses in both centralized laboratories and point-of-care settings.

Central environmental protection inspection and green technology innovation: empirical analysis based on the mechanism and spatial spillover effects.

In this study, the central environmental protection inspection (CEPI) policy is considered a quasi-natural experiment. Based on the data of 216 Chinese cities from 2008 to 2018, the influence of CEPI on green technology innovation (GTI) is empirically examined mainly using difference-in-differences (DIDs), propensity score matching DID and spatial DID methods. The results indicate that CEPI can effectively promote GTI. Regarding different types of GTI, CEPI mainly promoted utilitarian GTI. Regarding the mechanism, CEPI significantly promotes local GTI mainly through the increase of environmental protection expenditure and research and development investment. Considering the dynamic marginal effect, CEPI starts to significantly promote GTI in the second year after the policy implementation but exhibited no effects in the third year. The extended study shows that GTI effect of CEPI only occurs in small-medium cities and big cities. Furthermore, there is a certain beggar-thy-neighbor effect between inspected and uninspected cities. Finally, the spatial decomposition of CEPI effects shows that the inhibitory effect of CEPI on GTI mainly occurs in the neighboring uninspected cities, while CEPI has no evident inhibition on GTI in neighboring inspected cities.