Conditional replication and secretion of hepatitis B virus genome uncover the truncated 3' terminus of encapsidated viral pregenomic RNA.

IMPORTANCE: The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3' terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3' truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3' DR1, respectively, indicating the 3' DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3' unprotected terminus, which is independent of pgRNA length and the 3' terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics.

Ozone- and Hydroxyl Radical-Induced Degradation of Micropollutants in a Novel UVA-LED-Activated Periodate Advanced Oxidation Process.

In this study, novel light emitting diode (LED)-activated periodate (PI) advanced oxidation process (AOP) at an irradiation wavelength in the ultraviolet A range (UVA, UVA-LED/PI AOP) was developed and investigated using naproxen (NPX) as a model micropollutant. The UVA-LED/PI AOP remarkably enhanced the degradation of NPX and seven other selected micropollutants with the observed pseudo-first-order rate constants ranging from 0.069 ± 0.001 to 4.50 ± 0.145 min-1 at pH 7.0, demonstrating a broad-spectrum micropollutant degradation ability. Lines of evidence from experimental analysis and kinetic modeling confirmed that hydroxyl radical (•OH) and ozone (O3) were the dominant species generated in UVA-LED/PI AOP, and they contributed evenly to NPX degradation. Increasing the pH and irradiation wavelength negatively affected NPX degradation, and this could be well explained by the decreased quantum yield (ΦPI) of PI. The degradation kinetics of NPX by the UVA-LED/PI AOP in the presence of water matrices (i.e., chloride, bicarbonate, and humic acid) and in real waters were examined, and the underlying mechanisms were illustrated. A total of nine transformation products were identified from NPX oxidation by the UVA-LED/PI AOP, mainly via hydroxylation, dealkylation, and oxidation pathways. The UVA-LED/PI AOP proposed might be a promising technology for the treatment of micropollutants in aqueous solutions. The pivotal role of ΦPI during light photolysis of PI may guide the future design of light-assisted PI AOPs.

Selective Synthesis of ß-Ketonitriles via Catalytic Carbopalladation of Dinitriles.

A practical, convenient, and highly selective method of synthesizing ß-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.

Severe acute respiratory infection risk following glucocorticosteroid treatment in uncomplicated influenza-like illness resulting from pH1N1 influenza infection: a case control study.

BACKGROUND: Current studies regarding glucocorticosteroid treatment of influenza have only estimated risk of critical illness or death which can be easily confounded by timing of treatment administration. We used severe acute respiratory infection (sARI) as an endpoint and investigated risk associated with receiving glucocorticosteroids before sARI onset. METHODS: sARI cases were defined as influenza-like illness (ILI) with pH1N1 infection and respiratory distress. Controls were defined as pH1N1 cases other than sARI and randomly selected from the community. We compared glucocorticosteroids and other medications used before sARI onset using a matched case control study adjusted for age group as well as underlying disease. Time-dependent risk and dose responses at different time periods over the course of sARI cases were also examined. RESULTS: Of the sARI cases, 34% received glucocorticosteroids before sARI onset compared to 3.8% of controls during equivalent days (ORM-H = 17,95%CI = 2.1-135). Receiving glucocorticosteroids before sARI onset increased risk of developing subsequent critical illness or death (ORM-H = 5.7,95%CI = 1.6-20.2), and the ORM-H increased from 5.7 to 8.5 for continued glucocorticosteroid use after sARI onset. However, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness (ORM-H = 1.1,95%CI = 0.3-4.6). Each increase in glucocorticosteroids dose of 1 mg/kg/day before sARI onset resulted in an increase of 0.62 (R2 = 0.87) in the pMEWS score at the time of sARI onset. CONCLUSIONS: Early glucocorticosteroid treatment increased risk of sARI and subsequent critical illness or death; however, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness.

Novel sunlight-induced monochloramine activation system for efficient microcontaminant abatement.

As an eco-friendly and sustainable energy, solar energy has great application potential in water treatment. Herein, simulated sunlight was for the first time utilized to activate monochloramine for the degradation of environmental organic microcontaminants. Various microcontaminants could be efficiently degraded in the simulated sunlight/monochloramine system. The average innate quantum yield of monochloramine over the wavelength range of simulated sunlight was determined to be 0.068 mol/Einstein. With the determined quantum yield, a kinetic model was established. Based on the good agreement between the simulated and measured photolysis and radical contributions to the degradation of ibuprofen and carbamazepine, the major mechanism of monochloramine activation by simulated sunlight was proposed. Chlorine radical (Cl∙) and hydroxyl radical (HO∙) were major radicals responsible for microcontaminant degradation in the system. Moreover, the model facilitated a deep investigation into the effects of different reaction conditions (pH, monochloramine concentration, and water matrix components) on the degradation of ibuprofen and carbamazepine, as well as the roles of the involved radicals. The differences between simulated and measured degradation data of each microcontaminant under all conditions were less than 10 %, indicating the strong reliability of the model. The model could also make good prediction for microcontaminant degradation in the natural sunlight/monochloramine system. Furthermore, the formation of disinfection byproducts (DBPs) was evaluated at different oxidation time in simulated sunlight/monochloramine with and without post-chloramination treatment. In real waters, organic components showed more pronounced suppression on microcontaminant degradation efficiency than inorganic ions. This study provided a systematic investigation into the novel sunlight-induced monochloramine activation system for efficient microcontaminant degradation, and demonstrated the potential of the system in practical applications.

Markovnikov Hydrochlorination of Unactivated Alkenes with FeCl3 via a HAT/XAT Sequence.

Hydrochlorination of alkenes is a practical strategy for accessing organic chlorides. Herein, we report the hydrochlorination of unactivated alkenes via a hydrogen atom transfer/halogen atom transfer process using earth-abundant and biocompatible FeCl3 as a chlorine source under extraordinarily mild reaction conditions. The protocol is easy to operate with notable features such as excellent chemoselectivity, remarkable efficiency, a broad substrate scope, and good functional group tolerance. Importantly, the synthetic utility is highlighted by scaled-up reactions, late-stage derivatizations of products, and the modification of sulfonamides.

Matching periodate peak absorbance by far UVC at 222 nm promotes the degradation of micropollutants and energy efficiency.

Periodate (PI)-based advanced oxidation processes have gained increasing interest. This study for the first time elevates the light-activation capacity of PI by using far UVC at 222 nm (UV222/PI) without extra chemical inputs. The effectiveness and the underlying mechanisms of UV222/PI for the remediation of micropollutants were studied by selecting atenolol (ATL) as a representative. PI possessed a high molar absorption coefficient of 9480-6120 M-1 cm-1 at 222 nm in the pH range of 5.0-9.0, and it was rapidly decomposed by UV222 with first-order rate constants of 0.0055 to 0.002 s-1. ATL and the six other organic compounds were effectively degraded by the UV222/PI process under different conditions with the fluence-based rate constants generally two to hundred times higher than by UVA photolysis. Hydroxyl radical and ozone were confirmed as the major contributors to ATL degradation, while direct photolysis also played a role at higher pH or lower PI dosages. Degradation pathways of ATL were proposed including hydroxylation, demethylation, and oxidation. The high energy efficiency of the UV222/PI process was also confirmed. This study provides a cost-effective and convenient approach to enhance PI light-response activity for the treatment of micropollutants.

Unraveling the role of Mn(V)/Mn(III) in the enhanced permanganate oxidation under Vis-LED radiation.

A novel approach of visible light-emitting diode (Vis-LED) radiation was employed to activate permanganate (Mn(VII)) for efficient organic micropollutant (OMP) removal. The degradation rates of OMPs by Vis-LED/Mn(VII) were 2-5.29 times higher than those by Mn(VII) except for benzoic acid and atrazine. Increasing wavelengths (445-525 nm) suppressed the degradation of diclofenac (DCF) and 4-chlorophenol (4-CP) owing to the decreased quantum yields of Mn(VII). Comparatively, light intensity and Mn(VII) dosage had a positive effect on the degradation of DCF and 4-CP. Experimental data revealed that Mn(V) dominated the DCF degradation whereas Mn(III) was the active oxidant in the 4-CP degradation. Mn(V) and Mn(III) formed from the photo-decomposition of Mn(VII), meanwhile, Mn(III) also formed from the Mn(V) photo-decomposition. The increase in solution pH inhibited DCF degradation but had a positive impact on 4-CP degradation, mainly due to the changing speciation of DCF and 4-CP. Inorganic anions (Cl- and HCO3-) had little impact on DCF and 4-CP degradation, while humic acid (HA) showed a positive impact because of the π-π interaction between HA and DCF/4-CP. The transformation products of DCF and 4-CP were identified and transformation pathways were proposed. Finally, the Vis-LED/Mn(VII) exhibited great degradation performance in various authentic waters. Overall, this study boosts the development of Mn(VII)-based oxidation processes.

Role of bipyridyl in enhancing ferrate oxidation toward micropollutants.

Enhancing Fe(VI) oxidation ability by generating high-valent iron-oxo species (Fe(IV)/Fe(V)) has attracted continuous interest. This work for the first time reports the efficient activation of Fe(VI) by a well-known aza-aromatic chelating agent 2,2'-bipyridyl (BPY) for micropollutant degradation. The presence of BPY increased the degradation constants of six model compounds (i.e., sulfamethoxazole (SMX), diclofenac (DCF), atenolol (ATL), flumequine (FLU), 4-chlorophenol (4-CP), carbamazepine (CBZ)) with Fe(VI) by 2 - 6 folds compared to those by Fe(VI) alone at pH 8.0. Lines of evidence indicated the dominant role of Fe(IV)/Fe(V) intermediates. Density functional theory calculations suggested that the binding of Fe(III) to one or two BPY molecules initiated the oxidation of Fe(III) to Fe(IV) by Fe(VI), while Fe(VI) was reduced to Fe(V). The increased exposures of Fe(IV)/Fe(V) were experimentally verified by the pre-generated Fe(III) complex with BPY and using methyl phenyl sulfoxide as the probe compound. The presence of chloride and bicarbonate slightly affected model compound degradation by Fe(VI) in the presence of BPY, while a negative effect of humic acid was obtained under the same conditions. This work demonstrates the potential of N-donor heterocyclic ligand to activate Fe(VI) for micropollutant degradation, which is instructive for the Fe(VI)-based oxidation processes.

Refinement of kinetic model and understanding the role of dichloride radical (Cl2•-) in radical transformation in the UV/NH2Cl process.

The ultraviolet/monochloramine (UV/NH2Cl) process is an emerging advanced oxidation process with promising prospects in water treatment. Previous studies developed kinetic models of UV/NH2Cl for simulating radical concentrations and pollutant degradation. However, the reaction rate constants of Cl2•- with bicarbonate and carbonate (kCl2•-, HCO3- and kCl2•-, CO32-) were overestimated in literature. Consequently, when dosing 1 mM chloride and 1 mM bicarbonate, the current models of UV/NH2Cl severely under-predicted the experimental concentrations of three important radicals (i.e., hydroxyl radical (HO•), chlorine radical (Cl•), and dichloride radical (Cl2•-)) with great deviations (> 90 %). To investigate this issue, the transformation reactions among these three radicals in UV/NH2Cl were systematically studied. For the first time, it was found that in addition to Cl•, Cl2•- was also an important parent radical of HO• in the presence of chloride, and chloride could effectively compensate the inhibitory effect of bicarbonate on HO• generation in the system. Moreover, reactions and rate constants in current models were scrutinized from corresponding literature, and the reaction rate constants of Cl2•- with bicarbonate and carbonate (kCl2•-, HCO3- and kCl2•-, CO32-) were reevaluated to be 1.47 × 105 and 3.78 × 106 M-1s-1, respectively, by laser flash photolysis. With the newly obtained rate constants, the refined model could accurately simulate concentrations of all three radicals under different chloride and bicarbonate dosages with satisfactory deviations (< 30 %). Meanwhile, the refined model performed much better in predicting pollutant degradation and radical contribution compared with the unrefined model (with the previously estimated kCl2•-, HCO3- and kCl2•-, CO32-). The results of this study enhanced the accuracy and applicability of the kinetic model of UV/NH2Cl, and deepened the understanding of radical transformation in the process.

Suppression of bladder cancer growth by adeno-associated virus vector-mediated combination of HSV-TK and endostatin in vitro.

BACKGROUND: Gene therapy may offer a new tool for the treatment of bladder cancer. Previously, we have shown a significant antitumor effect in bladder cancer xenografts in a nude mouse model using intratumoral herpes simplex virus thymidine (HSV-TK) and endostatin gene monotherapy. OBJECTIVES: Given the high vascularity of human bladder cancer and the ability of HSV-TK or endostatin monotherapy to eradicate the tumors, we decided to test a novel combination of cytotoxic and antiangiogenic gene therapy using HSV-TK and endostatin adeno-associated viruses (AAV) in vitro. METHODS: We constructed the plasmid AAV-TK-IRES-Endostatin (pAAV-TIE) and packaged the AAV particles containing gene fragments of HSV-TK and endostatin. The combination anticancer effect of recombinant AAV-TIE (rAAV-TIE) was measured in vitro while rAAV-HSV-TK and rAAV-Endostatin were used as control groups. RESULTS: The inverted terminal repeat sequences were amplified using only one primer and the fragment between two ITRs of pAAV-TIE measuring about 4 kb, which indicated a stable sequence of pAAV-TIE. Three clear bands representing the AAV capsid proteins VP1, VP2, and VP3 could be seen on both lanes against a very low background, which demonstrated that chloroform extraction could effectively extract contaminants from rAAV stock without significant loss of the rAAV. In vitro, our results found that the transduction efficiency, measured from GFP-transduced tumors, was about 62%. The combination therapy led to an obvious apoptosis of bladder tumor cells compared with single HSV-TK or endostatin treatment. CONCLUSIONS: We concluded that the inhibition of angiogenesis using endostatin gene transfer, together with the cytotoxic HSV-TK gene therapy, resulted in a significant antitumor effect in vitro compared to the single gene based therapy in BTCC.

Potent antitumor activity of the combination of HSV-TK and endostatin by adeno-associated virus vector for bladder cancer in vivo.

BACKGROUND: Gene therapy may offer a new tool for the treatment of bladder cancer. Previously, we have shown a significant antitumor effect in bladder cancer xenografts in a nude mouse model using intratumoral herpes simplex virus thymidine (HSV-TK) and endostatin gene monotherapy. METHODS: Given the high vascularity of human bladder cancer and the ability of HSV-TK or endostatin monotherapy to eradicate the tumors, we decided to test a novel combination of cytotoxic and antiangiogenic gene therapy using intratumorally delivered HSV-TK and endostatin adeno-associated viruses (AAV). We constructed plasmid AAV-TK-IRES-Endostatin (pAAV-TIE) and packaged the AAV particles containing gene fragments of HSV-TK and endostatin. The combined anticancer effect of recombinant AAV-TIE (rAAV-TIE) was measured in vivo with rAAV-HSV-TK and rAAV-Endostatin as the control groups. RESULTS: The inverted terminal repeat sequence was amplified using only one primer and the fragment between two ITRs of pAAV-TIE measuring about 4 kb, which indicated a stable sequence of pAAV-TIE. Three clear bands representing the AAV capsid proteins VP1, VP2, and VP3 could be seen on both lanes against a very low background, which demonstrated that chloroform extraction could effectively extract contaminants from rAAV stock without significant loss of the rAAV. In vivo, our results showed that the tumors in mice injected with the rAAV-TIE not only took significantly longer to emerge but also that their growth, once established, was significant slower than that of tumors grown with single HSV-TK or endostatin treated animals. CONCLUSIONS: We concluded that the inhibition of angiogenesis using endostatin gene transfer, together with the cytotoxic HSV-TK gene therapy, resulted in a significant antitumor effect compared to the single gene based therapy in BTCC.

Photolysis of chlorite by solar light: An overlooked mitigation pathway for chlorite and micropollutants.

Chlorite (ClO2-) is an undesirable toxic byproduct commonly produced in the chlorine dioxide and ultraviolet/chlorine dioxide oxidation processes. Various methods have been developed to remove ClO2- but require additional chemicals or energy input. In this study, an overlooked mitigation pathway of ClO2- by solar light photolysis with a bonus for simultaneous removal of micropollutant co-present was reported. ClO2- could be efficiently decomposed to chloride (Cl-) and chlorate by simulated solar light (SSL) at water-relevant pHs with Cl- yield up to 65% at neutral pH. Multiple reactive species including hydroxyl radical (•OH), ozone (O3), chloride radical (Cl•), and chlorine oxide radical (ClO•) were generated in the SSL/ClO2- system with the steady-state concentrations following the order of O3 (≈ 0.8 µΜ) > ClO• (≈ 4.4 × 10-6 µΜ)> •OH (≈ 1.1 × 10-7 µΜ)> Cl• (≈ 6.8 × 10-8 µΜ) at neutral pH under investigated condition. Bezafibrate (BZF) as well as the selected six other micropollutants was efficiently degraded by the SSL/ClO2- system with pseudofirst-order rate constants ranging from 0.057 to 0.21 min-1 at pH 7.0, while most of them were negligibly degraded by SSL or ClO2- treatment alone. Kinetic modeling of BZF degradation by SSL/ClO2- at pHs 6.0 - 8.0 suggested that •OH contributed the most, followed by Cl•, O3, and ClO•. The presence of water background components (i.e., humic acid, bicarbonate, and chloride) exhibited negative effects on BZF degradation by the SSL/ClO2- system, mainly due to their competitive scavenging of reactive species therein. The mitigation of ClO2- and BZF under photolysis by natural solar light or in realistic waters was also confirmed. This study discovered an overlooked natural mitigation pathway for ClO2- and micropollutants, which has significant implications for understanding their fate in natural environments.

Efficient removal of p-arsanilic acid and arsenite by Fe(II)/peracetic acid (Fe(II)/PAA) and PAA processes.

The widespread occurrence of p-arsanilic acid (p-ASA) in natural environments poses big threats to the biosphere due to the generation of toxic inorganic arsenic (i.e., As(III) and As(V), especially As(III) with higher toxicity and mobility). Oxidation of p-ASA or As(III) to As(V) followed by precipitation of total arsenic using Fe-based advanced oxidation processes demonstrated to be a promising approach for the treatment of arsenic contamination. This study for the first time investigated the efficiency and inherent mechanism of p-ASA and As(III) oxidation by Fe(II)/peracetic acid (Fe(II)/PAA) and PAA processes. p-ASA was rapidly degraded by the Fe(II)/PAA process within 20 s at neutral to acidic pHs under different conditions, while it was insignificantly degraded by PAA oxidation alone. Lines of evidence suggested that hydroxyl radicals and organic radicals generated from the homolytic OO bond cleavage of PAA contributed to the degradation of p-ASA in the Fe(II)/PAA process. p-ASA was mainly oxidized to As (V), NH4+, and p-aminophenol by the Fe(II)/PAA process, wherein the aniline group and its para position were the most vulnerable sites. As(III) of concern was likely generated as an intermediate during p-ASA oxidation and it could be readily oxidized to As(V) by the Fe(II)/PAA process as well as PAA alone. The in-depth investigation demonstrated that PAA alone was effective in the oxidation of As(III) under varied conditions with a stoichiometric molar ratio of 1:1. Efficient removal (> 80%) of total arsenic during p-ASA oxidation by Fe(II)/PAA process or during As(III) oxidation by PAA process with additional Fe(III) in synthetic or real waters were observed, mainly due to the adsorptive interactions of amorphous ferric (oxy)hydroxide precipitates. This study systematically investigates the oxidation of p-ASA and As(III) by the Fe(II)/PAA and PAA processes, which is instructive for the future development of arsenic remediation technology.

Contact pattern, current immune barrier, and pathogen virulence determines the optimal strategy of further vaccination.

Background: The current outbreak of novel coronavirus disease 2019 has caused a serious disease burden worldwide. Vaccines are an important factor to sustain the epidemic. Although with a relatively high-vaccination worldwide, the decay of vaccine efficacy and the arising of new variants lead us to the challenge of maintaining a sufficient immune barrier to protect the population. Method: A case-contact tracking data in Hunan, China, is used to estimate the contact pattern of cases for scenarios including school, workspace, etc, rather than ordinary susceptible population. Based on the estimated vaccine coverage and efficacy, a multi-group vaccinated-exposed-presymptomatic-symptomatic-asymptomatic-removed model (VEFIAR) with 8 age groups, with each partitioned into 4 vaccination status groups is developed. The optimal dose-wise vaccinating strategy is optimized based on the currently estimated immunity barrier of coverage and efficacy, using the greedy algorithm that minimizes the cumulative cases, population size of hospitalization and fatality respectively in a certain future interval. Parameters of Delta and Omicron variants are used respectively in the optimization. Results: The estimated contact matrices of cases showed a concentration on middle ages, and has compatible magnitudes compared to estimations from contact surveys in other studies. The VEFIAR model is numerically stable. The optimal controled vaccination strategy requires immediate vaccination on the un-vaccinated high-contact population of age 30-39 to reduce the cumulative cases, and is stable with different basic reproduction numbers ( R 0 ). As for minimizing hospitalization and fatality, the optimized strategy requires vaccination on the un-vaccinated of both aged 30-39 of high contact frequency and the vulnerable older. Conclusion: The objective of reducing transmission requires vaccination in age groups of the highest contact frequency, with more priority for un-vaccinated than un-fully or fully vaccinated. The objective of reducing total hospitalization and fatality requires not only to reduce transmission but also to protect the vulnerable older. The priority changes by vaccination progress. For any region, if the local contact pattern is available, then with the vaccination coverage, efficacy, and disease characteristics of relative risks in heterogeneous populations, the optimal dose-wise vaccinating process will be obtained and gives hints for decision-making.

The overlooked role of Cr(VI) in micropollutant degradation under solar light irradiation.

Hexavalent chromium (Cr(VI)) is ubiquitous in natural environments, whereas its role in the transformation of coexisting contaminants may have been overlooked. In this work, it was reported for the first time that the irradiation of Cr(VI) by solar light (solar light/Cr(VI) system) could effectively degrade various micropollutants with different structures. The removal efficiency of selected micropollutants was increased by 13.3-64.8% by the solar light/Cr(VI) system compared to that by direct solar photolysis. Meanwhile, the oxidation rates were enhanced by 2.2-21.5 folds, while they were negligible by Cr(VI) oxidation alone. Experiments by specific scavengers, probe compounds, fluorescence absorbance, and electron spin resonance analysis demonstrated that hydroxyl radical (•OH) was the major reactive species in the solar light/Cr(VI) system. Further experiments showed that the generation of •OH was closely related to the intermediate Cr(V) generated from Cr(VI) reduction, and Cr(V) could be re-oxidized back to Cr(VI). Increasing solution pH negatively affected model micropollutant (carbamazepine (CBZ)) degradation by the solar light/Cr(VI) system, mainly due to the decreased quantum yield of •OH at higher pH. Coexisting sulfate ions showed negligible effect on CBZ degradation in the solar light/Cr(VI) system, while the presence of bicarbonate, chloride, and humic acid inhibited CBZ degradation to varying degrees, owing to their diverse scavenging effects on •OH. Furthermore, moderate CBZ degradation was also achieved by natural solar light photolysis of Cr(VI). This study demonstrated the pivotal role of Cr(VI) in the transformation of micropollutants under solar irradiation, which advances the understanding of the fate of micropollutants in natural environments.

Enhanced hydroxyl radical generation for micropollutant degradation in the In2O3/Vis-LED process through the addition of periodate.

Periodate (PI) as an oxidant has been extensively studied for organic foulants removal in advanced oxidation processes. Here PI was introduced into In2O3/Vis-LED process to enhance the formation of ·OH for promoting the degradation of organic foulants. Results showed that the addition of PI would significantly promote the removal of sulfamethoxazole (SMX) in the In2O3/Vis-LED process (from 9.26% to 100%), and ·OH was proved to be the dominant species in the system. Besides, the process exhibited non-selectivity in the removal of different organic foulants. Comparatively, various oxidants (e.g., peroxymonosulfate, peroxydisulfate, and hydrogen peroxide) did not markedly promote the removal of SMX in the In2O3/Vis-LED process. Electrochemical analyses demonstrated that PI could effectively receive photoelectrons, thus inhibiting the recombination of photogenerated electron-hole (e-/h+) pairs. The holes then oxidized the adsorbed H2O to generate ·OH, and the PI converted to iodate at the same time. Additionally, the removal rate of SMX reduced from 100% to 17.2% as Vis-LED wavelengths increased from 440 to 560 nm, because of the low energy of photons produced at longer wavelengths. Notably, the species of PI do not affect its ability to accept electrons, resulting in the degradation efficiency of SMX irrespective of pH (4.0-10.0). The coexistence of inorganic cations and anions (such as Cl-, CO32-/HCO3-, SO42-, Ca2+, and Mg2+) also had an insignificant effect on SMX degradation. Furthermore, the process also showed excellent degradation potential in real water. The proposed strategy provides a new insight for visible light-catalyzed activation of PI and guidance to explore green catalytic processes for high-efficiency removal of various organic foulants.

Potent antitumour activity of the combination of HSV-TK and endostatin armed oncolytic adeno-associated virus for bladder cancer in vitro and in vivo.

BACKGROUND: Gene therapy may offer a new tool for the treatment of bladder cancer. Previously, we have shown a significant antitumour effect in bladder cancer xenografts in a nude mouse model using intratumoural herpes simple virus thymidine (HSV-TK) and Endostatin gene therapy. OBJECTIVES: Given the high vascularity of human bladder cancer and the ability of HSV-TK or Endostatin monotherapy to eradicate the tumours, we decided to test a novel combination of cytotoxicity and antiangiogenisis gene therapy using intratumourally delivered HSV-TK and Endostatin adeno-associated viruses (AAVs). METHODS: We constructed plasmid AAV-TK-IRES-Endostatin (pAAV-TIE) and packaged the AAV particles contain gene fragments of HSV-TK and Endostatin. The function of HSV-TK and Endostatin was evaluated separately in vitro via T24 bladder tumour cells and human umbilical vein endothelial (HUVEC) cells. The combination anticancer effect of recombinant AAV-TIE (rAAV-TIE) was measured in vivo while rAAV-HSV-TK and rAAV-Endostatin as control groups. RESULTS: In vitro, rAAV-TIE was found to induce a significant increase in apoptosis in HUVEC cells equally as rAAV-Endostatin and confirmed that the inhibition of endothelial cells mediated by rAAV-TIE was associated with the apoptotic process. rAAV-TIE was found to induce a significant increase in apoptosis in T24 cells equally as rAAV-HSV-TK and confirmed that the inhibition of T24 cells mediated by rAAV-TIE was associated with the apoptotic process too. In vivo, our results showed that the tumours in mice injected with the rAAV-TIE not only took significantly longer to emerge but also that their growth, once established, was significant slower than that of tumours grown, compared with single HSV-TK or Endostatin treated animals. CONCLUSIONS: We concluded that the inhibition of angiogenesis using Endostatin gene transfer, together with the cytotoxicity HSV-TK gene therapy, resulted in a significant antitumour effect compared to the single gene based therapy in BTCC. The results warrant further development of the combination gene therapy, and suggest that this approach, directed towards systemic efficiency, could be used as an additional treatment for human BTCC.

Advances in new antivirals for chronic hepatitis B.

ABSTRACT: Chronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.

Integrated Rabies Surveillance - Hunan Province, China, 2020.

Introduction: The objective of this paper was to assess the epidemiology of rabies in Hunan Province, analyze the associated factors, understand the status of prevention and treatment after rabies exposure, evaluate the effectiveness of prevention and treatment, and provide a scientific basis for formulating effective prevention and control measures. Methods: The surveillance data of rabies in Hunan Province in 2020 were collected and analyzed by descriptive epidemiological method. Results: In 2020, a total of 59 cases of rabies were reported in Hunan Province, with an incidence rate of 0.09/100,000. Overall, 42 cases (71.19%) were due to animal bites and 43 cases (72.88%) were of grade III. The proportion of hand and combined injury of hand was the highest (40.68%). A total of 603,261 cases of rabies exposure were reported from the rabies post-exposure prophylaxis (PEP) clinic in Hunan Province. Dogs were the main animal causing injuries, accounting for 74.21%. Only 83,418 (13.84%) of the animals had a clear immune history, and a total of 11 dog attacks were reported in Hunan Province. The average immunity rate of dogs in the whole province was 30.98%. In 2020, 554 dogs were sampled in the whole province; 20 of them were positive for a positivity rate of 3.61%. Conclusions: Rabies in Hunan Province in 2020 had a relatively low prevalence. Failure to treat wounds, immunoglobulin injections, and vaccination after exposure were the main causes of rabies. Therefore, post-exposure management of rabies should be further strengthened to reduce the risk of rabies for high-risk populations.