The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity.

The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here, we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.

Constructing a Carbon-Encapsulated Carbon Composite Material with Hierarchically Porous Architectures for Efficient Capacitive Storage in Organic Supercapacitors.

Hierarchical porous activated carbon (HPAC) materials with fascinating porous features are favored for their function as active materials for supercapacitors. However, achieving high mass-loading of the HPAC electrodes remains challenging. Inspired by the concepts of carbon/carbon (C/C) composites and hydrogels, a novel hydrogel-derived HPAC (H-HPAC) encapsulated H-HPAC (H@H) composite material was successfully synthesized in this study. In comparison with the original H-HPAC, it is noticed that the specific surface area and pore parameters of the resulting H@H are observably decreased, while the proportions of nitrogen species are dramatically enhanced. The free-standing and flexible H@H electrodes with a mass-loading of 7.5 mg/cm2 are further prepared for electrochemical measurements. The experiments revealed remarkable reversible capacitance (118.6 F/g at 1 mA/cm2), rate capability (73.9 F/g at 10 mA/cm2), and cycling stability (76.6% of retention after 30,000 cycles at 5 mA) are delivered by the coin-type symmetric cells. The cycling stability is even better than that of the H-HPAC electrode. Consequently, the findings of the present study suggest that the nature of the HPAC surface is a significant factor affecting the corresponding capacitive performances.

Feasibility and Short-Term Stability of Portal Vein Infusion Port Placement by Transjugular Access.

Six pigs underwent implantation of a portal vein infusion port by transjugular access. The technical success rate was 100% (n = 6), with no surgical complications or deaths. At 1 month after implantation, the catheter tip had moved from the splenic vein to the main portal vein, while the catheter protruded into the right ventricle through the right atrium in all cases. Hence, the infusion port system has not been used in clinical practice due to its obvious displacement after implantation. However, this study provides a new idea for future exploration of portal vein infusion pathways.

Single Pt-Pd Bimetallic Nanoparticle Electrode: Controllable Fabrication and Unique Electrocatalytic Performance for the Methanol Oxidation Reaction.

Understanding the electrocatalytic activity at single nanoparticles/nanoclusters level is extremely important. In this work, a method for the electro-deposition of single Pt-Pd nanoparticles (NPs) is described using a single nanopore electrode as a template. The electro-deposition process was investigated carefully and the results show that the process is controlled by diffusion and electro-crystallization process, simultaneously, and the glass sheath property around the nanopore has a large impact on the formation of single Pt-Pd NPs due to the "edge effect". The prepared single Pt-Pd NPs exhibit excellent electrocatalytic activity in the methanol oxidation reaction, which can be used to screen electrocatalysts with high efficiency for utility in the energy field.

Initial Results from SQUID Sensor: Analysis and Modeling for the ELF/VLF Atmospheric Noise.

In this paper, the amplitude probability density (APD) of the wideband extremely low frequency (ELF) and very low frequency (VLF) atmospheric noise is studied. The electromagnetic signals from the atmosphere, referred to herein as atmospheric noise, was recorded by a mobile low-temperature superconducting quantum interference device (SQUID) receiver under magnetically unshielded conditions. In order to eliminate the adverse effect brought by the geomagnetic activities and powerline, the measured field data was preprocessed to suppress the baseline wandering and harmonics by symmetric wavelet transform and least square methods firstly. Then statistical analysis was performed for the atmospheric noise on different time and frequency scales. Finally, the wideband ELF/VLF atmospheric noise was analyzed and modeled separately. Experimental results show that, Gaussian model is appropriate to depict preprocessed ELF atmospheric noise by a hole puncher operator. While for VLF atmospheric noise, symmetric α-stable (SαS) distribution is more accurate to fit the heavy-tail of the envelope probability density function (pdf).

A topology control algorithm for fusion networks based on link quality.

To extend the network life, an ordinal potential game is introduced into network topology control, and a network topology control algorithm based on the Theil entropy measure is designed by improving the revenue function. The revenue function is based on the Theil entropy measure, whose factors are in the residual energy of the nodes and their neighbors. By using a primary payoff function that considers all initial network factors and a secondary one that addresses connectivity in case of reduced residual energy, a segmentation function can calculate the model's payoff. Simulation experiments show that compared to the existing game algorithms of 3DK-RNG, DEBA, and EFPC, the proposed algorithm can effectively eliminate redundant links, reduce node degree and network link length, balance node energy consumption, enhance network load, and extend the network life cycle.•A Network Topology Control Algorithm Based on the Fusion of Thiel Entropy and Ordinal Potential Games.•A network topology control method for extending the network lifecycle is successfully established.•It proposes that the performance of the fusion topology control algorithm is significantly superior to other single algorithms in the paper.

The Safety and Efficacy of Hepatic Arterial Infusion Chemotherapy Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapies for the Treatment of Intermediate and Advanced Hepatocellular Carcinoma Unsuitable for Transarterial Chemoembolization.

Objective: To investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) for intermediate and advanced HCC that are unsuitable for transarterial chemoembolization (TACE). Methods: We conducted a retrospective analysis of data from patients with TACE-unsuitable HCC who were receiving triple therapy from January 2020 to December 2021 at two medical centers. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rates (ORR), disease control rates (DCR), and incidence of adverse events (AEs). Results: A total of 55 patients were enrolled in the study with median treatment periods of 4 and 6 for HAIC and PD-(L)1 inhibitors, respectively. The median OS and PFS were 15.0 and 10.0 months, respectively, with a median follow-up of 11.0 months (range: 4.0-27.5 months). According to the mRECIST criteria, the optimal ORR was 43.6% (24/55) and the DCR was 61.8% (34/55). The incidence of AEs was 58.2%, with grade 3 and above accounting for 20.0%; elevated AST (18.2%), hyperbilirubinemia (16.4%), and thrombocytopenia (16.4%) were most common. There were no treatment-related fatalities and all AEs were effectively managed. Multifactorial analysis showed that NLR > 3.82 (HR 2.380, 95% CI 1.116-2-5.079, P = 0.025), ECOG 1 (HR 2.906, 95% CI 1.373-6.154, P = 0.005), and extrahepatic metastases (HR 8.373, 95% CI 3.492-20.078, P < 0.001) were associated with the median OS. Conclusion: Triple therapy with HAIC, PD-(L)1 inhibitors, and MTT was safe and effective for patients with intermediate and advanced HCC for TACE-unsuitability.

Large Paraumbilical Vein Shunts Increase the Risk of Overt Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Placement.

Background: This study aimed to evaluate whether a large paraumbilical vein (L-PUV) was independently associated with the occurrence of overt hepatic encephalopathy (OHE) after the implantation of a transjugular intrahepatic portosystemic shunt (TIPS). Methods: This bi-center retrospective study included patients with cirrhotic variceal bleeding treated with a TIPS between December 2015 and June 2021. An L-PUV was defined in line with the following criteria: cross-sectional areas > 83 square millimeters, diameter ≥ 8 mm, or greater than half of the diameter of the main portal vein. The primary outcome was the 2-year OHE rate, and secondary outcomes included the 2-year mortality, all-cause rebleeding rate, and shunt dysfunction rate. Results: After 1:2 propensity score matching, a total of 27 patients with an L-PUV and 54 patients without any SPSS (control group) were included. Patients with an L-PUV had significantly higher 2-year OHE rates compared with the control group (51.9% vs. 25.9%, HR = 2.301, 95%CI 1.094−4.839, p = 0.028) and similar rates of 2-year mortality (14.8% vs. 11.1%, HR = 1.497, 95%CI 0.422−5.314, p = 0.532), as well as variceal rebleeding (11.1% vs. 13.0%, HR = 0.860, 95%CI 0.222−3.327, p = 0.827). Liver function parameters were similar in both groups during the follow-up, with a tendency toward higher shunt patency in the L-PUV group (p = 0.067). Multivariate analysis indicated that having an L-PUV (HR = 2.127, 95%CI 1.050−4.682, p = 0.037) was the only independent risk factor for the incidence of 2-year OHE. Conclusions: Having an L-PUV was associated with an increased risk of OHE after a TIPS. Prophylaxis management should be considered during clinical management.

Low-dose heparin retention in temporary hemodialysis double-lumen catheter does not increase catheter occlusion and might reduce risk of bleeding.

BACKGROUND: The objective of this study was to assess the impact of heparin concentration retained in temporary double-lumen catheters on bleeding risk. METHODS: Activated partial thromboplastin time (aPTT) was measured in patients hemodialyzed via double-lumen catheters. Heparin solutions of 5,000 U/ml (group 1, n = 95) and 1,000 U/ml (group 2, n = 89) were randomly retained in catheters after placement and each hemodialysis (HD) session. Blood transfusion, bleeding episodes, and changes of hematocrit were recorded. RESULTS: The aPTT at the beginning of HD or 10 min after heparin lock was significantly prolonged, which was more prominent in the 5,000 U/ml group, whereas the aPTT declined to baseline values at the end of HD or before the next dialysis session in both groups. Infection and occlusion rates were similar in both groups. More patients suffered from major bleeding and prominent decline of hematocrit in the 5,000 U/ml group. CONCLUSIONS: Low-dose heparin (1,000 U/ml) retention in double-lumen catheters for temporary HD maintains comparable catheter patency and might reduce the bleeding risk.

A neglected posterior fracture dislocation of the shoulder with ipsilateral distal humeral shaft fracture.

BACKGROUND: Cases of posterior dislocation or fracture-dislocation of the shoulder are rare. A combination of posterior dislocation and ipsilateral humeral shaft fracture, especially a distal third one, is even rarer. In such injuries, the diagnosis of shoulder dislocation may be missed because great attention is usually given to the fractured humerus. OBJECTIVES: We present this case report to raise awareness among emergency physicians of this manner of injury. CASE REPORT: We present a case report of a 30-year-old woman who had posterior fracture dislocation of the right shoulder with ipsilateral distal humeral shaft fracture. The shaft fracture was initially evaluated, internally reduced, and fixed, whereas the posterior fracture-dislocation of the shoulder was not recognized. A belated diagnosis was established 1 month after the operation, when a computed tomography scan was performed because the patient reported continuous pain and limited range of motion of the shoulder. A second reduction was performed to reduce the dislocation. The patient had partial functional recovery 1 year later. CONCLUSIONS: Consideration of this condition, coupled with thorough and appropriate physical and radiological examinations, could lead to improved recognition of such cases.

A phase 3 clinical trial of MINHAI PCV13 in Chinese children aged from 7 months to 5 years old.

BACKGROUND: Pneumococcus lead to various kinds of invasive disease such as pneumonia, otitis media, meningitis, bacteremia and so on. It has been a great threat to children under 5. A new 13-valent pneumococcal conjugate vaccine (PCV13) with carrier tetanus toxoid and diphtheria toxoid was developed by MINHAI, aiming to prevent pneumococcus infection. In this study, we reported the safety and immunogenicity of MINHAI PCV13 in Chinese children aged from 7 months to 5 years old. METHODS: A randomized, double-blinded, parallelized phase III clinical trial was operated in 900 participants. Haemophilus influenzae type B conjugate vaccine (Hib) served as negative control. PCV13 and Hib were intramuscular injected to participants at a ratio of 2:1. Local and systemic adverse events (AEs) and severe adverse events (SAEs) were recorded to evaluate the safety of PCV13. Blood samples were collected before and after immunization for the detecting of serotype-specific anti-polysaccharide immunoglobulin (Ig)G and opsonophagocytosis assay (OPA). The proportion of IgG concentration ≥ 0.35 µg/mL (IgG positive rate), IgG geometric mean concentration (GMC), OPA geometric mean titer (GMT), and other indicators were analyzed to evaluate the immunogenicity of PCV13. RESULTS: During the study period, no PCV13 associated SAE happened. Incidences of several AEs in PCV13 groups were higher than the Hib groups, but most of them were mild or moderate. For all 13 serotypes, IgG and OPA indicators of the PCV13 groups were generally superior to the Hib groups, and the differences were mostly statistically significant, which indicates that MINHAI PCV13 can effectively induce pneumococcal specific antibody. CONCLUSION: The study demonstrates that MINHAI PCV13 has sufficient immunogenicity and safety in Chinese children aged from 7 months to 5 years old. CLINICAL TRIAL REGISTRATION: NCT02494999.

Protective Effect of Pyrroloquinoline Quinone on TNF-α-induced Mitochondrial Injury in Chondrocytes.

Osteoarthritis (OA) is a degenerative disease characterized by matrix degradation and cell death leading to a gradual loss of articular cartilage integrity. As a bacterial synthesis of quinine, pyrroloquinoline quinone (PQQ) is a strong redox cofactor with a variety of biological benefits, including antioxidant, anti-inflammation-induced mitochondrial metabolism regulation. This study was designed to investigate the effect of PQQ on TNF-α-induced mitochondrial damage in chondrocytes. Chondrocytes isolated from C57BL/6 mice were exposed to TNF-α 50 ng/mL, TNF-α 50 ng/mL + PQQ 10 µmol/L for 24 h. Then, morphological study, functional study and mechanism study were taken. The results revealed TNF-α-induced chondrocyte mitochondrion damage could be reduced by application of PQQ, evidenced by elevated number of mitochondria, well-kept mtDNA integrity, preserved ATP level, reestablished mitochondrial membrane potential, and prevented mitochondrial function. The present work strongly suggests that the mitochondrion is an important target for OA chondrocyte damage induced by TNF-α and the PQQ protection from this damage ameliorates mitochondrial dysfunction induced by TNF-α. PQQ might be a potential chemical for OA intervention.

Performance of artificial intelligence for prognostic prediction with the albumin-bilirubin and platelet-albumin-bilirubin for cirrhotic patients with acute variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt.

PURPOSE: The aim of this study was to validate and compare the prognostic performance of the albumin-bilirubin (ALBI) grade, platelet-albumin-bilirubin (PALBI) grade, Child-Pugh (CP) grade, and Model for End-Stage Liver Disease (MELD) score in predicting the 1-year variceal rebleeding probability using artificial intelligence for patients with cirrhosis and variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt (TIPS) procedures. MATERIALS AND METHODS: This dual-center retrospective study included two cohorts, with patients enrolled between January 2016 and September 2018 in the training cohort and January 2017 and September 2018 in the validation cohort. In the training cohort, independent risk factors associated with the 1-year variceal rebleeding probability were identified using univariate and multivariate logistic analyses. ALBI-, PALBI-, Child-Pugh-, and MELD-based nomograms and an artificial neural network (ANN) model were established and validated internally in the training cohort and externally in the validation cohort, which included patients with variceal bleeding who were treated with preventive TIPS. RESULTS: A total of 259 patients were included. The median follow-up periods were 24.1 and 18.9 months, and the 1-year variceal rebleeding rates were 12.3% (14/114) and 10.3% (15/145) in the training and validation cohorts, respectively. In the training cohort, all four variables were identified as independent risk factors. Four nomograms were then established and showed comparable prognostic performances after internal (C-index: 0.879, 0.829, 0.874, and 0.798) and external (C-index: 0.720, 0.719, 0.718, and 0.703) validation. The ANN demonstrated that these four variables had comparable importance in predicting the 1-year variceal rebleeding probability. CONCLUSION: None of the four variables are optimal in predicting the 1-year variceal rebleeding probability for patients with cirrhosis and variceal bleeding undergoing early TIPS.

Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay.

Pseudotyped viruses are useful virological tools because of their safety and versatility. On the basis of a vesicular stomatitis virus (VSV) pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in biosafety level 2 facilities. Compared with the binding antibody test, the neutralization assay could discriminate the protective agents from the antibody family. This protocol includes production and titration of the SARS-CoV-2 S pseudotyped virus and the neutralization assay based on it. Various types of samples targeting virus attachment and entry could be evaluated for their potency, including serum samples derived from animals and humans, monoclonal antibodies and fusion inhibitors (peptides or small molecules). If the pseudotyped virus stock has been prepared in advance, it will take 2 days to get the potency data for the candidate samples. Experience in handling cells is needed before implementing this protocol.

Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2.

Pseudoviruses are useful virological tools because of their safety and versatility, especially for emerging and re-emerging viruses. Due to its high pathogenicity and infectivity and the lack of effective vaccines and therapeutics, live SARS-CoV-2 has to be handled under biosafety level 3 conditions, which has hindered the development of vaccines and therapeutics. Based on a VSV pseudovirus production system, a pseudovirus-based neutralization assay has been developed for evaluating neutralizing antibodies against SARS-CoV-2 in biosafety level 2 facilities. The key parameters for this assay were optimized, including cell types, cell numbers, virus inoculum. When tested against the SARS-CoV-2 pseudovirus, SARS-CoV-2 convalescent patient sera showed high neutralizing potency, which underscore its potential as therapeutics. The limit of detection for this assay was determined as 22.1 and 43.2 for human and mouse serum samples respectively using a panel of 120 negative samples. The cutoff values were set as 30 and 50 for human and mouse serum samples, respectively. This assay showed relatively low coefficient of variations with 15.9% and 16.2% for the intra- and inter-assay analyses respectively. Taken together, we established a robust pseudovirus-based neutralization assay for SARS-CoV-2 and are glad to share pseudoviruses and related protocols with the developers of vaccines or therapeutics to fight against this lethal virus.

Patellofemoral MRI Alterations Following Single Bundle ACL Reconstruction with Hamstring Autografts Are Associated with Quadriceps Femoris Atrophy.

High incidence of patellofemoral pain and patellofemoral joint osteoarthritis was found following anterior cruciate ligament (ACL) reconstruction. The unstability of patellofemoral joint might be an important contribution factor. This study was designed to define the relationship between the unstability of patellofemoral joint and quadriceps femoris atrophy. Twenty patients underwent MRI scan before ACL reconstruction and every two weeks after surgery, until 12 weeks. The merchant's patellar congruence angle, lateral inclination angle, and quadriceps femoris muscle cross-sectional area were measured and the relationship between the changes of angles and the ratio of quadriceps femoris atrophy was studied by multiple regression analysis. Significant quadriceps femoris atrophy was observed after ACL reconstruction during the follow-up period of 12 weeks. The merchant's patellar congruence angle and lateral inclination angle significantly changed after surgery. The alterations of the merchant's patellar congruence angle were significantly correlated with the atrophy ratio of vastus medialis (coefficient=-15.76) and vastus lateralis (coefficient=8.35) during the follow-up period of 12 weeks. The alterations of lateral inclination angle were significantly correlated with the atrophy ratio of vastus medialis (coefficient=20.62), vastus lateralis (coefficient=-11.38) and rectus femoris (coefficient=-0.469) during the follow-up period 12 weeks. To sum up, ACL reconstruction can alleviate the dysfunction of patellofemoral joint to a certain extent. But, the unbalanced atrophy of quadriceps femoris once again destroyed the stability of patellofemoral joint following the operation, which might be one cause of patellofemoral joint pain and early onset of osteoarthritis after ACL reconstruction. So, rehabilitation training that focuses on quadriceps femoris especially the vastus medialis shortly following operation is suggested.

[VOCs Emission Inventory of Anthropogenic Sources in Jiaxing].

The anthropogenic volatile organic compounds (VOCs) emissions inventory in Jiaxing for 2015 was established by collecting comprehensive activity data of anthropogenic sources and adopting scientific and reasonable estimation methods and emissions factors. Results showed that the total VOCs emissions in Jiaxing for 2015 amounted to 10.21×104 t, of which 78.15%, 12.08%, 5.83%, 3.24%, 0.26%, and 0.44% was contributed by industrial sources, vehicles, domestic sources, oil storage and transport, waste disposal, and burning of agricultural crop residues, respectively. Packaging and printing industries, the surface coating industry, the dyeing industry, chemical materials manufacturers, and the petrochemical industry are the most important VOCs-emitting industries. Haining, Tongxiang, and Pinghu were the three cities with the highest emissions amounts, which contributed 50% of the total VOCs emissions. The average emissions intensity of VOCs in Jingkai, Haining, and Nanhu exceeded 30 t·km-2.

MRI observations of patellar tendon length change after ACL reconstruction with hamstring autografts.

The post-operative patellar tendon length was studied to evaluate the possible tendon length change after anterior cruciate ligament (ACL) reconstruction with hamstring autografts. The Insall-Salvati index, modified Insall-Salvati index, curved modified Insall-Salvati index and Caton-Deschamps index were observed by MRI during a follow-up period of 12 weeks on 20 ACL reconstructed knees. The results showed no patellar baja or alta pre-existed on those ACL injured patients. After a follow-up period of 12 weeks, no patellar tendon length change was observed. It is suggested that the change of patella was not the primary reason that may contribute to the premature patellofemoral joint osteoarthritis after ACL reconstruction.

Pulmonary hypertension in patients on chronic hemodialysis and with heart failure.

Pulmonary hypertension (PH) is linked to chronic kidney disease. However, few studies have examined the prevalence, risk factors, or outcomes of PH in patients with chronic hemodialysis and concomitant heart failure. This retrospective cohort study enrolled 160 patients with a history of acute decompensated heart failure after maintenance hemodialysis therapy. All patients were prospectively observed until December 2013 or death. PH was defined as pulmonary artery systolic pressure >35 mmHg, as determined through echocardiography. Fifty-one (32%) patients had PH, more of whom were female (70% vs. 52%, P = 0.04). The patients with PH had a lower body mass index (21.8 vs. 23.0, P = 0.03), higher cardiothoracic ratio (55% vs. 52%, P = 0.006), larger left atrium (38.5 vs. 35.7 mm, P = 0.01), and an increased proportion of mitral regurgitation (MR) (73% vs. 38%, P < 0.001) compared with the patients who did not have PH. In the multivariate regression analysis, MR was associated most strongly with PH (odds ratio 3.75, 95% confidence interval [CI]: 1.67-8.43, P = 0.001). In the multivariate Cox proportional hazard models, PH was related independently to all-cause mortality (hazard ratio [HR], 3.11; 95% CI, 1.53-6.31; P = 0.002) and combined cardiovascular events (HR, 2.71; 95% CI, 1.66-4.44; P < 0.001) after the model was adjusted for conventional cardiovascular risk factors. PH is related to MR and independently associated with increased all-cause mortality and cardiovascular events in patients with chronic hemodialysis and heart failure.

Pyrroloquinoline quinone enhances regeneration of transected sciatic nerve in rats.

OBJECTIVE: To investigate the effect of pyrroloquinoline quinone (PQQ) on nerve regeneration of transected sciatic nerve in animal models. METHODS: Forty SD rats weighing 220-240 g were randomized into a PQQ group (n = 20) and a control group (n = 20). Each animal underwent sciatic nerve transection operation. After the operation, PQQ 0.5 ml (250 microg/Kg) was injected at the operation site in the PQQ group, while the same volume of normal saline was delivered in the control group. Nerve functional evaluation, electrophysiological index recording were carried out according to the experimental design. Newly generated nerve specimens were harvested 12 weeks postoperatively for morphological studies. RESULTS: In the PQQ group there was a good nerve regeneration and the sciatic nerve function, sciatic nerve function index, electrophysiological index and morphological appearance were superior to the control group (P < 0.05). CONCLUSIONS: PQQ has a remarkable effect in enhancing nerve regeneration of transected peripheral nerve.