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Background: Ending the global COVID-19 pandemic requires efficacious therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, the emerging Omicron sublineages largely escaped the neutralization of current authorized monoclonal antibody therapies. Here we report a tetravalent bispecific antibody ISH0339, as a potential candidate for long-term and broad protection against COVID-19. Methods: We report here the making of ISH0339, a novel tetravalent bispecific antibody composed of a pair of non-competing neutralizing antibodies that binds specifically to two different neutralizing epitopes of SARS-CoV-2 receptor-binding domain (RBD) and contains an engineered Fc region for prolonged antibody half-life. We describe the preclinical characterization of ISH0339 and discuss its potential as a novel agent for both prophylactic and therapeutic purposes against SARS-CoV-2 infection. Results: ISH0339 bound to SARS-CoV-2 RBD specifically with high affinity and potently blocked the binding of RBD to the host receptor hACE2. ISH0339 demonstrated greater binding, blocking and neutralizing efficiency than its parental monoclonal antibodies, and retained neutralizing ability to all tested SARS-CoV-2 variants of concern. Single dosing of ISH0339 showed potent neutralizing activity for treatment via intravenous injection and for prophylaxis via nasal spray. Preclinical studies following single dosing of ISH0339 showed favorable pharmacokinetics and well-tolerated toxicology profile. Conclusion: ISH0339 has demonstrated a favorable safety profile and potent anti-SARS-CoV-2 activities against all current variants of concern. Furthermore, prophylactic and therapeutic application of ISH0339 significantly reduced the viral titer in lungs. Investigational New Drug studies to evaluate the safety, tolerability and preliminary efficacy of ISH0339 for both prophylactic and therapeutic purposes against SARS-CoV-2 infection have been filed.

Combined chemo-immuno-photothermal therapy based on ursolic acid/astragaloside IV-loaded hyaluronic acid-modified polydopamine nanomedicine is a promising strategy for the treatment of non-small cell lung cancer (NSCLC) metastasis.

In this work, ordinary epoxy coatings were modified by hydrophobic nanoSiO2 and hydroxyl PDMS to construct ultrahydrophobic epoxy coatings for corrosion protection and self-cleaning of phosphatized Q235 carbon steel. Ordinary epoxy polymer coating was fabricated via polyaddition reaction between E44 (bisphenol A epoxy resin oligomer) and DDM (4,4-diaminodiphenyl methane). The microscopic morphologies of coatings showed that many SiO2 nanoparticles were presented on the surface of ultrahydrophobic epoxy coating. Through static water contact angle measurement, the modified epoxy coating displayed ultrahydrophobicity with a water contact angle of approximately 150°. However, adding too much nanoSiO2 caused cracks on the modified epoxy coating, which deteriorated the corrosion resistance of the coating. According to the corrosion test results, the modified coating added with 6.7 wt% hydrophobic nanoSiO2 and chemically modified with hydroxyl PDMS showed the best corrosion protection performance, which was reflected by the high impedance of approximately 109 Ω·cm2 after 50 d immersion in 3.5 wt% NaCl (aq.). Besides, the coating also presented good self-cleaning performance. The coating extracted from the slurry still remained clean without any contamination.

Polyurethane chain was successfully grafted onto carbon nanotubes, affording polyurethane-functionalized multiwalled carbon nanotubes (P-MWCNTs) with super-hydrophobic property, which shows improved abrasive resistance obviously and enhanced thermal conductivity for natural rubber (NR) vulcanizate. Under the optimized conditions, the akron abrasion loss of NR vulcanizate combined with 5 parts per hundred rubber (5 phr) P-MWCNTs is 0.9 cm3/1.61 km compared to 2.96 cm3/1.61 km of pristine NR vulcanizate. The thermal conductivity of NR vulcanizate combined with 5 phr P-MWCNTs has been improved by 40.3% compared to that of pristine NR vulcanizate. The decreased height of the maximum tan δ peak shows that P-MWCNTs can reduce the heat buildup and damping capability of NR/P-MWCNTs composites. The good dispersion of P-MWCNTs with a continuous network, particularly at high loading (5 phr) in the NR composites, was evidenced from transmission electron microscopy (TEM).

The SARS-CoV-2 virus has infected more than 261 million people and has led to more than 5 million deaths in the past year and a half

Corrosion of carbon steel causes many losses, hazards, and contaminations to our daily life. In this article, epoxy synergistically added with hydrophobic nano-silica and graphene was prepared to provide corrosion protection for carbon steel. Graphene can act as filler to improve the corrosion resistance of epoxy, but the aggregation of graphene severely affects its application. Embedding hydrophobic nano-silica into graphene sheets contributes to the good dispersity of graphene in an epoxy matrix. Besides, SiO2 can also act as another filler to improve corrosion resistance. Hence, the synergistical addition of hydrophobic nano-silica and graphene into epoxy can provide better corrosion resistance for modified epoxy coating. A scanning electron microscope was used to investigate the microstructures of modified epoxy coating. Coating wettability was measured by a static contact angle measurement instrument. The anticorrosive behaviors of modified coatings were measured by an electrochemical workstation. The corrosion mechanism was analyzed by equivalent circuits simulation. According to the results, the modified coating with impedance of about 108 Ω·cm2 (10 mHz) at 100 d immersion still showed excellent anticorrosive performance. In general, epoxy doped with hydrophobic nano-silica and graphene displays better corrosion protection than epoxy without modification.

Pt/Co/Hf multilayers were prepared by magnetron sputtering, and the magnetic anisotropy was effectively regulated by Hf thickness and heat treatment in Pt/Co/Hf films. The interface microstructures were characterized. The influence of the interface microstructure on magnetic properties was studied. The results show that the magnetic anisotropy in Pt/Co/Hf films is closely related to the interface microstructure, which is influenced by Hf thickness and the heat treatment temperature. Microstructure analysis shows that after the Pt(3)/Co(1.5)/Hf(1) film is heat-treated, the CoOx content increases, more CoPt(111) forms, the interface is smoother and sharper, and the roughness of the Co/Hf interface decreases. Several factors work together to cause the magnetic anisotropy of the sample to change from in-plane magnetic anisotropy (IMA)to perpendicular magnetic anisotropy (PMA).

Background and purposeSpinal dural arteriovenous fistulas located in the lumbosacral region are rare and present with nonspecific clinical signs. The purpose of this study was to find out the specific radiologic features of these fistulas.MethodsWe retrospectively reviewed the clinical and radiological data of 38 patients diagnosed with lumbosacral spinal dural arteriovenous fistulas in our institution from September 2016 to September 2021. All patients underwent time-resolved contrast-enhanced three-dimensional MRA and DSA examinations, and were treated with either endovascular or neurosurgical strategies.ResultsMost of the patients (89.5%) had motor or sensory disorders in both lower limbs as the first symptoms. On MRA, the dilated filum terminale vein or radicular vein was seen in 23/30 (76.7%) patients with lumbar spinal dural arteriovenous fistulas and 8/8 (100%) patients with sacral spinal dural arteriovenous fistulas. T2W intramedullary abnormally high signal intensity areas were found in all lumbosacral spinal dural arteriovenous fistula patients, with involvement of the conus present in 35/38 (92.1%) patients. The “missing piece sign” in the intramedullary enhancement area was seen in 29/38 (76.3%) patients.ConclusionDilatation of the filum terminale vein or radicular vein is powerful evidence for diagnosis of lumbosacral spinal dural arteriovenous fistulas, especially for sacral spinal dural arteriovenous fistulas. T2W intramedullary hyperintensity in the thoracic spinal cord and conus, and the missing-piece sign could be indicative of lumbosacral spinal dural arteriovenous fistula.

Convectively generated cold pools play a crucial role in the convection initiation and development, but observations of their vertical structure are insufficient. In this study, quantitative vertical evolutions of cold pools during a high-impact heavy rainfall event near the south coast of China were examined using observations from a 356-m high Shenzhen Met-Tower, and their potential impacts on heavy rainfall were further discussed through high-resolution surface station network and radar observations. On 11 April 2019, heavy precipitation occurred near metropolitan Shenzhen, lasting for 50 min at its southern downtown and resulting in 11 deaths. During this event, a shallow cold pool was first observed by the tower and yielded a long-lasting cooling of 2.6 K. Approximately one hour later, another deeper cold pool accompanied by a squall line was added from the west. This addition resulted in a more abrupt and intense surface temperature deficit (5.1 K) and stronger gusty winds (23 m/s). When the two cold pools collided near Shenzhen, the low-level winds converged at their intersection, dynamically enhancing the heavy-rain-producing squall line. Moreover, the collision of the two cold pools reduced the temperature gradient at the northern edge of the merged cold pool, which could inhibit development of the squall line. The area south of the squall line became a relatively favorable environment for convection initiation, given the warm and moist oceanic environment. Consequently, the squall line turned northeast–southwest, forming a training line mode that was nearly parallel to the eastward movement. This training line mode prolonged the precipitation duration in the southern downtown area.

Since the 1980s, Japanese scholars have been doing field research on ethnic minorities in China. Along with its rich and colorful national culture as well as its ecological culture, Guangxi has piqued the interest of Japanese scholars. In order to provide a multi-dimensional observation perspective and useful reference for the sustainable development of contemporary ethnic minorities in Guangxi, this paper analyses and discusses the research methods, discipline fields, and academic contributions of Japanese research on ethnic minorities in Guangxi over the last 40 years.

In this work, an easy, green, noncovalent surface modification of pristine graphene (GR) was carried out using a single-step method between sodium carboxymethyl cellulose (CMC) and pristine GR, resulting in the formation of a modified CMC-GR (CGR) dispersion with 15% nanosheet content, the first reported in water. Results obtained from thermogravimetry analysis (TGA), Raman spectroscopy, and atomic force microscopy (AFM) confirm that the CMC modifier is successfully decorated on the pristine GR surface. Analyses of transmittance spectrum, zeta potential and transmittance electron microscopy (TEM) images reveal that the modified CGR has a high degree of dispersion. More importantly, the pristine GR is insoluble, while the modified CGR-3, mixed with 1.1 wt% CMC modifier, is easily well dispersed in water and has good flowability, and no sedimentation is observed after more than 3 months.

Herein, we demonstrate that the stable AlScN model with wurtzite structure is described by small/negligible vacancy concentrations and minimal localized distortions.

Mechanism research of nanozymes has always been of great interest since their emergence as outstanding mimics of friable natural enzymes. An important but rarely mentioned issue in mechanism research of nanozymology is the inhibitory effect of nanozymes. And conventional nanozymes with various active sites hinder the mechanism research, while single-atom Fe-N-C nanozymes with similar active sites to natural enzymes exhibit structural advantages. Herein, we synthesized Fe single-atom nanozymes (Fe-SANs) with ultrahigh oxidase-like activity and found that a common analgesic-antipyretic drug 4-acetamidophenol (AMP) had inhibitory effects for the oxidase-like activity of Fe-SANs. We investigated the inhibitory effects in detail and demonstrated that the inhibition type was reversible mixed-inhibition with inhibition constants (

Herein, a method is described for pyrolysis associated with in situ ultrasonic synthesis of flower-like p-n-type BiOCl/g-C3N4 assembled with nanosheets for enhancing the visible-light degradation of Rhodamine B (RhB). The formation process, structure, microscopic morphology, and photocatalytic activity of the samples were investigated in detail. In addition, the results of simulated visible light-driven photocatalytic experiments showed that, compared with pure g-C3N4, the BiOCl (20 wt %)/g-C3N4 composite photocatalyst exhibited better degradation ability with a maximum k value of 0.109 min−1, and the most significant total removal rate of RhB was up to 99 %, which is about ninefold in comparison with pure g-C3N4. Finally, the enhanced photocatalytic activities of the products could be attributed to the suitable band structures between the BiOCl/g-C3N4 composite with rich oxygen vacancies for the effective separation of photogenerated electron–hole pairs.

Chronic wound is a common complication for diabetic patients, which entails substantial inconvenience, persistent pain, and significant economic burden to patients. However, current clinical treatments for diabetic chronic wounds remain unsatisfactory. A prolonged but ineffective inflammation phase in chronic wounds is the primary difference between diabetic chronic wounds and normal wounds. Herein, we present an effective antioxidative system (MOF/Gel) for chronic wound healing of diabetic rats through integrating a metal organic framework (MOF) nanozyme with antioxidant enzyme-like activity with a hydrogel (Gel). MOF/Gel can continuously scavenge reactive oxygen species to modulate the oxidative stress microenvironment in diabetic chronic wounds, which leads to a natural transition from the inflammation phase to the proliferation phase. Impressively, the efficacy of one-time-applied MOF/Gel was comparable to that of the human epidermal growth factor Gel, a widely used clinical drug for various wound treatments. Such an effective, safe, and convenient MOF/Gel system can meet complex clinical demands.

Double hydrosilylation of alkynes represents a straightforward method to synthesize bis(silane)s, yet it is challenging if α-substituted vinylsilanes act as the intermediates. Here, a cobalt-catalyzed regiodivergent double hydrosilylation of arylacetylenes is reported for the first time involving this challenge, accessing both vicinal and geminal bis(silane)s with exclusive regioselectivity. Various novel bis(silane)s containing Si-H bonds can be easily obtained. The gram-scale reactions could be performed smoothly. Preliminarily mechanistic studies demonstrated that the reactions were initiated by cobalt-catalyzed α-hydrosilylation of alkynes, followed by cobalt-catalyzed β-hydrosilylation of the α-vinylsilanes to deliver vicinal bis(silane)s, or hydride-catalyzed α-hydrosilylation to give geminal ones. Notably, these bis(silane)s can be used for the synthesis of high-refractive-index polymers (n

Long non-coding RNAs (lncRNAs) play an essential role in diverse biological processes and disease development. Accurate classification of lncRNAs and mRNAs is important for the identification of tissue- or disease-specific lncRNAs. Here, we present our tool LncDC (Long non-coding RNA detection) that is able to accurately predict lncRNAs with an XGBoost model using features extracted from RNA sequences, secondary structures, and translated proteins. Benchmarking experiments showed that LncDC consistently outperformed six state-of-the-art tools in distinguishing lncRNAs from mRNAs. Notably, the use of sequence and secondary structure (SASS) k-mer score features and flexible ORF features improved the classification capability of LncDC. We anticipate that LncDC will definitely promote the discovery of more and novel disease-specific lncRNAs. LncDC is implemented in Python and freely available at https://github.com/lim74/LncDC.

Sewage sludge and waste biomass are unavoidable byproducts of municipal and industrial processes. Both materials have significant carbon contents. Activated coke with a developed pore structure can be obtained after its physical activation. In this study, sewage sludge and waste poplar bark were used as precursor materials to prepare activated coke by steam, carbon dioxide gas, and their mixtures. The effects of different concentrations of activation gas on the activated coke product were investigated. Through nitrogen adsorption analysis, it was found that activated coke has a higher specific surface area and better pore structure when activated in gas containing 20% steam. The activated coke prepared by carbon dioxide gas activation has higher microporosity than that prepared by steam activation. Infrared spectrum analysis shows that steam activation is beneficial to the formation of free hydroxyl functional groups. Through scanning electron microscopy analysis, the pores of activated coke prepared by steam activation appeared to extend deeper in the structure of the coke, while the pores of activated coke prepared by carbon dioxide activation appeared to have fine circular structures. The activated coke prepared by the activation of mixed gas appeared to have ablated particles on the surface due to the ablation of the pore structure. In order to prepare activated coke with excellent adsorption performance, the physical and chemical properties of activated coke under different activation conditions were studied in detail.

On-site hydrogen peroxide production through electrocatalytic and photocatalytic oxygen reduction reactions has recently attracted broad research interest. However, practical applications have thus far been plagued by the low activity and the requirement of complex equipment. Here, inspired by the process of biological hydrogen peroxide synthesis catalyzed by enzymes, we report a Pt-Au alloy to mimic the catalytic function of natural formate oxidase for hydrogen peroxide synthesis through aerobic oxidation of formic acid. The mass activity of the Pt-Au alloy is three times higher than that of formate oxidase. Density functional theory calculations revealed that the efficient dehydrogenation of formic acid and the high selectivity of the subsequent reduction of oxygen to hydrogen peroxide account for the high hydrogen peroxide productivity. In addition, the formic acid aqueous solution provides an acidic environment, which is conducive to the utilization of the in situ generated hydrogen peroxide for oxidation reactions, including C-H bond oxidation and sterilization.

Approximately 50–60% of patients with a clinical transient ischemic attack (TIA) do not have diffusion-weighted imaging (DWI) evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of diffusion kurtosis imaging (DKI) in the evaluation of patients with TIA who have normal DWI findings. From September 2014 to May 2017, a total of 179 consecutive patients with suspected TIA were eligible for enrollment in our study. The inclusion criteria were a confirmed diagnosis of TIA confirmed by a stroke neurologist, MRI (including DWI and DKI) within 24 h after symptom onset, no stroke history, and no DWI lesion. A follow-up DWI was performed to establish stroke recurrence within a period of 90 days. A total of 98 patients who had no lesions on the baseline DWI were included for data analysis. Of these 98 patients, 31 (31.6%) had positive findings on the initial DKI. In 29 of the 31 (93.5%) patients, the location of the abnormality observed on DKI was consistent with the clinical symptoms. During the 90-day follow-up period, 14 (14.3%) patients developed recurrent stroke. The prevalence of recurrent stroke was higher in the DKI-positive group than in the DKI-negative group (29.0% vs. 7.5%, p = 0.01). A comparison between the patients with and without recurrent stroke showed that an abnormality on the baseline DKI was associated with stroke recurrence. Furthermore, 8 of the 9 stroke patients in the DKI-positive group developed a new ischemic lesion in the artery territory corresponding to the initial DKI abnormality. The new findings suggest the predictive value of DKI on the recurrence of stroke in the patients with TIA who have negative findings on conventional DWI.

The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.

Natural organic matter (NOM) has always been considered the main precursor of disinfection by-products (DBPs) during the chlorine disinfection of drinking water. This research focuses on investigating the correlation between the functional group (carboxyl and carbonyl groups) content of NOM and the formation of trichloromethane (TCM) and chloral hydrate (CH). The quantitative determination of carboxyl groups, carbonyl groups, TCM, and CH were conducted during the drinking water treatment processes with different coagulant dosages and with/without pre-oxidation by KMnO4 or NaClO. The most appropriate coagulant for the removal of conventional components was polyaluminum chloride (PAC), and the dosage was 110 mg/L. Up to 43.7% and 14.5% of the carboxyl and carbonyl groups, respectively, were removed through the coagulation and sedimentation processes, which can be enhanced by increasing PAC dosage. The filtration process further increased the removal rates of these two functional groups to 59.8% and 33.5%, respectively. The formation potential of the TCM and CH decreased as the PAC dosage increased. Pre-oxidation by KMnO4 (0.8–1.0 mg/L) effectively controlled the formation of DBPs while increasing the carboxyl and carbonyl group content. Pre-oxidation by NaClO decreased the formation of TCM rather than CH, and a suitable amount (0.5–1.0 mg/L) decreased the carboxyl and carbonyl groups. It was found that there was a good linear correlation between carboxyl groups and TCM and CH. The linear fit R2 values of the carboxyl groups to TCM and CH were 0.6644 and 0.7957, respectively. The linear fit R2 values of the carbonyl groups to TCM and CH were 0.5373 and 0.7595, respectively.

The stability and wide temperature performance range of solid electrolytes are the keys to the development of high-energy density all-solid-state lithium-ion batteries. In this work, a PVDF-HFP-LiClO

In this work, we develop a level-set subdifferential error bound condition with an eye toward convergence rate analysis of a variable Bregman proximal gradient (VBPG) method for a broad class of nonsmooth and nonconvex optimization problems. It is proved that the aforementioned condition guarantees linear convergence of VBPG and is weaker than Kurdyka–Łojasiewicz property, weak metric subregularity, and Bregman proximal error bound. Along the way, we are able to derive a number of verifiable conditions for level-set subdifferential error bounds to hold, and necessary conditions and sufficient conditions for linear convergence relative to a level set for nonsmooth and nonconvex optimization problems. The newly established results not only enable us to show that any accumulation point of the sequence generated by VBPG is at least a critical point of the limiting subdifferential or even a critical point of the proximal subdifferential with a fixed Bregman function in each iteration, but also provide a fresh perspective that allows us to explore inner-connections among many known sufficient conditions for linear convergence of various first-order methods.

Phenyllactic acid (PLA) has gained a lot of attention due to its broad antimicrobial activity, but the mechanism of its antifungal action has been barely reported until now. Herein, the inhibitory activity of PLA against Aspergillus flavus spore germination and its mechanism were preliminarily investigated. Results indicated that PLA had a strong antifungal activity against A. flavus with the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of 6 and 12 mg/ml, respectively. As observed by scanning electron microscopy (SEM), the A. flavus spores displayed wrinkled and shrunken appearance after treatment with PLA. In addition, the permeability and integrity of A. flavus cell membrane were changed obviously after PLA treatment as indicated by the propidium iodide (PI) staining results, which was further confirmed by a rise in electric conductivity and increased leakage of intracellular protein and nucleic acid. Furthermore, reduced activities of mitochondrial ATPase and dehydrogenases caused by PLA were also observed in A. flavus spores, with a result of remarkable decrease in ATP synthesis. Therefore, it could be concluded that PLA was effective in inhibiting spore germination of A. flavus mainly by disrupting cell membrane and interfering with mitochondrial energy metabolism.

Patulin (PAT) is one of mycotoxins that usually contaminates apple juice, and it is not easily detoxified by cysteine (CYS) at room temperature due to the highly acidic conditions based on the Michael addition reaction. However, it could be effectively degraded by a heating treatment at 120 °C for 30 min in the presence of cysteine. In our study, a total of eight degradation products (DP A–H) were characterized and identified via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) in a negative ion mode, and their structures and formulas were proposed based on their accurate mass data. The fragmentation patterns of PAT and its degradation products were obtained from the MS/MS analysis. Meanwhile, the possible reaction mechanisms involved in the degradation of PAT were established and explained for the first time. According to the relation between the structure and toxicity of PAT, it could be deduced that the toxic effects of PAT degradation products were potentially much less than those of PAT-self.