Current Status and Challenges in Anti-Hepatitis B Virus Agents Based on Inactivation/Inhibition or Elimination of Hepatitis B Virus Covalently Closed Circular DNA.

There has been over half a century since the discovery of hepatitis B virus (HBV) to now, but approximately 300 million patients with chronic hepatitis B (CHB) still live in the world, resulting in about one million deaths every year. Although currently approved antivirals (e.g., nucleoside analogues) are effective at reducing HBV replication, they have almost no impact on the existing HBV covalently closed circular DNA (cccDNA) reservoir. HBV cccDNA is a critical obstacle to the complete elimination of the virus via antiviral therapy. The true cure of HBV infection requires the eradication of viral cccDNA from HBV-infected cells; thus, the development of new agents directly or indirectly targeting HBV cccDNA is urgently needed due to the limitations of current available drugs against HBV infection. In this regard, it is the major focus of current anti-HBV research worldwide via different mechanisms to either inactivate/inhibit (functional cure) or eliminate (complete cure) HBV cccDNA. Therefore, this review discussed and summarized recent advances and challenges in efforts to inactivate/silence or eliminate viral cccDNA using anti-HBV agents from different sources, such as small molecules (including epigenetic drugs) and polypeptides/proteins, and siRNA or gene-editing approaches targeting/attenuating HBV cccDNA via different mechanisms, as well as future directions that may be considered in efforts to truly cure chronic HBV infection. In conclusion, no breakthrough has been made yet in attenuating HBV cccDNA, although a number of candidates have advanced into the phase of clinical trials. Furthermore, the overwhelming majority of the candidates function to indirectly target HBV cccDNA. No outstanding candidate directly targets HBV cccDNA. Relatively speaking, CCC_R08 and nitazoxanide may be some of the most promising agents to clear HBV infection in small molecule compounds. Additionally, CRISPR-Cas9 systems can directly target HBV cccDNA for decay and demonstrate significant anti-HBV activity. Consequently, gene-editing approaches targeting HBV cccDNA may be one of the most promising means to achieve the core goal of anti-HBV therapeutic strategies. In short, more basic studies on HBV infection need to be carried out to overcome these challenges.

Advances in the Study of MG53 in Cardiovascular Disease.

Cardiovascular diseases represent a global health crisis, and understanding the intricate molecular mechanisms underlying cardiac pathology is crucial for developing effective diagnostic and therapeutic strategies. Mitsugumin-53 (MG53) plays a pivotal role in cell membrane repair, has emerged as a multifaceted player in cardiovascular health. MG53, also known as TRIM72, is primarily expressed in cardiac and skeletal muscle and actively participates in membrane repair processes essential for maintaining cardiomyocyte viability. It promotes k-ion currents, ensuring action potential integrity, and actively engages in repairing myocardial and mitochondrial membranes, preserving cardiac function in the face of oxidative stress. This study discusses the dual impact of MG53 on cardiac health, highlighting its cardioprotective role during ischemia/reperfusion injury, its modulation of cardiac arrhythmias, and its influence on cardiomyopathy. MG53's regulation of metabolic pathways, such as lipid metabolism, underlines its role in diabetic cardiomyopathy, while its potential to mitigate the effects of various cardiac disorders, including those induced by antipsychotic medications and alcohol consumption, warrants further exploration. Furthermore, we examine MG53's diagnostic potential as a biomarker for cardiac injury. Research has shown that MG53 levels correlate with cardiomyocyte damage and may predict major adverse cardiovascular events, highlighting its value as a biomarker. Additionally, exogenous recombinant human MG53 (rhMG53) emerges as a promising therapeutic option, demonstrating its ability to reduce infarct size, inhibit apoptosis, and attenuate fibrotic responses. In summary, MG53's diagnostic and therapeutic potential in cardiovascular diseases presents an exciting avenue for improved patient care and outcomes.

An injury-responsive mmp14b enhancer is required for heart regeneration.

Mammals have limited capacity for heart regeneration, whereas zebrafish have extraordinary regeneration abilities. During zebrafish heart regeneration, endothelial cells promote cardiomyocyte cell cycle reentry and myocardial repair, but the mechanisms responsible for promoting an injury microenvironment conducive to regeneration remain incompletely defined. Here, we identify the matrix metalloproteinase Mmp14b as an essential regulator of heart regeneration. We identify a TEAD-dependent mmp14b endothelial enhancer induced by heart injury in zebrafish and mice, and we show that the enhancer is required for regeneration, supporting a role for Hippo signaling upstream of mmp14b. Last, we show that MMP-14 function in mice is important for the accumulation of Agrin, an essential regulator of neonatal mouse heart regeneration. These findings reveal mechanisms for extracellular matrix remodeling that promote heart regeneration.

Effect of skinfold thickness on arm venous access port in cancer patients.

BACKGROUND: Currently, skinfold thickness in studies on arm venous access ports and the effect of venous access port application are unknown. MATERIALS AND METHODS: A total of 256 cancer patients who underwent primary venous access port placement in the Fourth Hospital of Hebei Medical University from September 2022 to March 2023 were selected as the study subjects. Two hundred fifty-six patients were divided into normal skinfold thickness group and high skinfold thickness group according to skinfold thickness. The success rate of primary catheterization of arm venous port catheterization, catheterization operation time, catheterization length and incidence rate of adverse reactions were compared. RESULTS: There was no significant difference in the basic data between the two groups. There was no significant difference in the success rate of primary catheterization between the two groups (p > 0.05), the catheterization operation time in the normal skinfold thickness group was significantly lower than that in the high skinfold thickness group (p < 0.05), the total length of the implanted catheter in the normal skinfold thickness group was significantly lower than that in the high skinfold thickness group (p < 0.05), and the incidence of adverse reactions in the normal skinfold thickness group was significantly lower than that in the high skinfold thickness group (p < 0.05). CONCLUSION: In cancer patients, skinfold thickness can significantly affect the application effect of arm venous port, and normal skinfold thickness for arm venous port has shorter operation time, total length of implanted catheter and lower incidence of adverse reactions.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020.

Objective: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. Methods: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. Results: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. Conclusion: The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

A regional cooperative reduction game model for air pollution control in North China.

Due to variations in economic scale, economic structure, and technological advancement across different Chinese provinces and cities, the cost of air pollution reduction differs significantly. Therefore, the total reduction cost can be decreased by capitalizing on these regional discrepancies in reduction cost to carry out cooperative emission reduction. In this paper, taking NOx reduction in North China as an example, a regional cooperative reduction game (CRG) model was constructed to minimize the total cost of emission reduction while achieving future emission reduction targets. The fair allocation of benefits from cooperation plays a crucial role in motivating regions to participate into the cooperation. A comprehensive mechanism of benefits allocation was proposed to achieve fair transferred compensation. The mechanism combines the consumption responsibility principle based on input-output theory and the Shapley value method based on game theory. Compared to the cost before the optimized collaboration, the CRG model will save 20.36% and 13.71% of the total reduction cost in North China, respectively, under the target of 17.68% NOx reduction by 2025 and 66.44% NOx reduction by 2035 relative to 2020. This method can be employed in other regions to achieve targets for air pollution reduction at minimum cost, and to motivate inter-regional cooperation with this practical and fair way of transferred compensation.

Health burden evaluation of industrial parks caused by PM2.5 pollution at city scale.

Industrial park is an important emission sector of PM2.5 pollution. Previous studies have provided valuable information on the impact of PM2.5 from industrial parks on human health, but relevant studies at city scale are limited. In this study, the health burden of industrial parks was evaluated based on PM2.5-related premature deaths and economic contributions. The premature deaths were calculated in terms of a novel research model by integrating the Bayesian maximum entropy (BME) model, weighted concentration-weighted trajectory (WCWT), and integrated exposure-response function (IER). Take Tianjin City for example, it was found that since the main diffusion direction of PM2.5 in Tianjin is from south to north, the industrial parks in the south of Tianjin and close to the central city with high population density have high health burden. These industrial parks need to be focused on or even relocated in the future. The research model can provide scientific basis for the health burden evaluation of industrial parks at city scale, so as to help local governments optimize the layout of industrial parks and formulate environmental responsibility management policies for industrial parks.

Fertilization can modify the enantioselective persistence of penthiopyrad in relation to the co-influence on soil ecological health.

Penthiopyrad is a widely used chiral fungicide for controlling rust and Rhizoctonia diseases. Development of optically pure monomers is an important strategy to realize amount reduction and increment effects of penthiopyrad, wherein, fertilizers as the co-exiting nutrient supplement may alter the enantioselective residues of penthiopyrad in soil. In our study, influences of urea, phosphate, potash, NPK compound, organic granular, vermicompost and soya bean cake fertilizers on enantioselective persistence of penthiopyrad were fully evaluated. This study demonstrated that R-(-)-penthiopyrad dissipated faster than S-(+)-penthiopyrad during 120 days. High pH, available nitrogen, invertase activities and reduced available phosphorus, dehydrogenase, urease, catalase activities were situated to benefit removing the concentrations of penthiopyrad and weakening enantioselectivity in soil. With respect to the impact of different fertilizers on soil ecological indicators, vermicompost contributed to enhanced pH. Urea and compound fertilizer played an absolute advantage in promoting available nitrogen. All fertilizers didn't go against available phosphorus. Dehydrogenase responded negatively to phosphate, potash and organic fertilizers. Urea increased invertase, besides, it and compound fertilizer both diminished urease activity. The catalase activity was not activated by organic fertilizer. Based on all the findings, soil application of urea and phosphate fertilizers was recommended and considered as a better option to exhibit high efficiency for the dissipation of penthiopyrad. The combined environmental safety estimation can effectively guide the treatment of fertilization soils in line with the nutrition requirements and pollution regulation from penthiopyrad.

Developing Personas of Gamers with Problematic Gaming Behavior among College Students Based on Qualitative Data of Gaming Motives and Push-Pull-Mooring.

Gaming is a popular but possibly problematic activity among college students. To distinguish gamers with potential problematic gaming behaviors (PGB) is crucial to mental health staff. Two studies were conducted that aimed to explore portraits of gamers with PGB in college campuses. The first study selected 20 college students, diagnosed with problematic gaming behaviors, from a longitudinal dataset and semi-structured interviews were conducted for a systematic description of long-term PGB. The second study selected four personas with the richest coding data of internet addiction and depression from 20 gamers. The profiles and life experiences of the personas showed changing processes of gaming motives and push-pull-mooring effects across the years. "Loss of purpose in life" and "desperate to escape from stress or boredom in the real world" were the important push effects. Mooring effects revealed their addiction or depression symptoms and the process of developing the addiction. The dynamics of "push", "pull", and "mooring" effects were clearly indicated in the results suggesting PGB might be a long-term coping strategy and a consequence of depression and loneliness. Dealing with depression and finding real-life goals could help PGB gamers to change the dynamics of their gaming motives and push-pull-mooring effects. The results may help develop interventions for gamers with problematic gaming behaviors.

Public Concern about Haze and Ozone in the Era of Their Coordinated Control in China.

In China, due to the implementation of the Action Plan for Prevention and Control of Air Pollution (APPCAP), the concentrations of PM2.5 (fine particulate matter) and severe haze in most cities have decreased significantly. However, at present, haze pollution in China has not been completely mitigated, and the problem of O3 (ozone) has become prominent. Therefore, the prevention and control of haze and O3 pollution have become important and noticeable issues in the field of atmospheric management. We used the Baidu search indices of "haze" and "ozone" to reflect public concerns about air quality and uncover different correlations between level of concern and level of pollution, and then we identified regions in China that require public attention. The results showed that (1) over the last decade, the search index of haze had a rapid trend of variation in line with changes in haze pollution, but that of O3 had a relatively slowly increasing trend; (2) the lag days between the peaks of public concern and the peaks of air pollution became increasingly shorter according to daily data analysis; and (3) 96 polluted cities did not receive sufficient public attention. Although periods of heavily haze-polluted weather, which affects visibility, have generated much public concern, periods of slight pollution have not received enough public attention. Public health protection and environmental participation regarding these periods of slight pollution in China deserve appropriate levels of attention.

Combined detection of urinary biomarkers noninvasively predicts extent of renal injury in patients with early diabetic kidney disease with kidney qi deficiency syndrome: A retrospective investigation.

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-ß-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.

Aiphanol, a multi-targeting stilbenolignan, potently suppresses mouse lymphangiogenesis and lymphatic metastasis.

The high incidence of lymphatic metastasis is closely related to poor prognosis and mortality in cancers. Potent inhibitors to prevent pathological lymphangiogenesis and lymphatic spread are urgently needed. The VEGF-C-VEGFR3 pathway plays a vital role in driving lymphangiogenesis and lymph node metastasis. In addition, COX2 in tumor cells and tumor-associated macrophages (TAMs) facilitates lymphangiogenesis. We recently reported that aiphanol, a natural stilbenolignan, attenuates tumor angiogenesis by repressing VEGFR2 and COX2. In this study, we evaluated the antilymphangiogenic and antimetastatic potency of aiphanol using in vitro, ex vivo and in vivo systems. We first demonstrated that aiphanol directly bound to VEGFR3 and blocked its kinase activity with an half-maximal inhibitory concentration (IC50) value of 0.29 µM in an in vitro ADP-GloTM kinase assay. Furthermore, we showed that aiphanol (7.5-30 µM) dose-dependently counteracted VEGF-C-induced proliferation, migration and tubular formation of lymphatic endothelial cells (LECs), which was further verified in vivo. VEGFR3 knockdown markedly mitigated the inhibitory potency of aiphanol on lymphangiogenesis. In 4T1-luc breast tumor-bearing mice, oral administration of aiphanol (5 and 30 mg· kg-1 ·d-1) dose-dependently decreased lymphatic metastasis and prolonged survival time, which was associated with impaired lymphangiogenesis, angiogenesis and, interestingly, macrophage infiltration. In addition, we found that aiphanol decreased the COX2-dependent secretion of PGE2 and VEGF-C from tumor cells and macrophages. These results demonstrate that aiphanol is an appealing agent for preventing lymphangiogenesis and lymphatic dissemination by synergistically targeting VEGFR3 and inhibiting the COX2-PGE2-VEGF-C signaling axis.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

A multi-targeting natural product, aiphanol, inhibits tumor growth and metastasis.

Cancer is one of the main causes of death in humans worldwide, the development of more effective anticancer drugs that can inhibit the malignant progression of cancer cells is of great significance. Aiphanol is a natural product identified from the seeds of Arecaceae and the rhizome of Smilax glabra Roxb. Our preliminary studies revealed that it had potential antiangiogenic and antilymphangiogenic activity by directly targeting VEGFR2/3 and COX2 in endothelial cells. However, the influence of aiphanol on cancer cells per se remains largely undefined. In this study, the effects and related mechanisms of aiphanol on cancer growth and metastasis were evaluated in vitro and in vivo. Acute toxicity assay and pharmacokinetic analysis were utilized to investigate the safety profile and metabolism characteristics of aiphanol. We revealed that aiphanol inhibited the proliferation of various types of cancer cells and the growth of xenograft tumors in mice and zebrafish models. The possible mechanism was associated with the inactivation of multiple kinases, including FAK, AKT and ERK, and the upregulation of BAX and cleaved caspase-3 to promote cancer cell apoptosis. Aiphanol significantly inhibited cancer cell migration and invasion, which was related to the inhibition of epithelial-mesenchymal transition (EMT) and F-actin aggregation. Aiphanol effectively attenuated the metastasis of several types of cancer cells in vivo. In addition, aiphanol exerted no significant toxicity and had fast metabolism. Collectively, we demonstrated the anticancer effects of aiphanol and suggested that aiphanol has potential as a safe and effective therapeutic agent to treat cancer.

Clinical Applications of Aneuploidies in Evolution of NSCLC Patients: Current Status and Application Prospect.

As one of the first characteristics of cancer cells, chromosomal aberrations during cell division have been well documented. Aneuploidy is a feature of most cancer cells accompanied by an elevated rate of mis-segregation of chromosomes, called chromosome instability (CIN). Aneuploidy causes ongoing karyotypic changes that contribute to tumor heterogeneity, drug resistance, and treatment failure, which are considered predictors of poor prognosis. Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, and its genome map shows extensive aneuploid changes. Elucidating the role of aneuploidy in the pathogenesis of LC will reveal information about the key factors of tumor occurrence and development, help to predict the prognosis of cancer, clarify tumor evolution, metastasis, and drug response, and may promote the development of precision oncology. In this review, we describe many possible causes of aneuploidy and provide evidence of the role of aneuploidy in the evolution of LC, providing a basis for future biological and clinical research.

Assessing public health and economic loss associated with black carbon exposure using monitoring and MERRA-2 data.

Black carbon (BC) exposure in China continues to be relatively high, prompting researchers to assess BC exposure levels using data from monitoring sites, satellite remote sensing, and models. However, data regarding the application of a combined strategy comprising the analysis of monitoring data and various types of data to simulate BC exposure levels are lacking. Hence, the current study seeks to estimate short- and long-term BC exposure levels by combining national monitoring data with data from the second Modern-Era Retrospective analysis for Research and Applications (MERRA-2). Furthermore, this study attempts to improve the spatio-temporal resolution of BC exposure levels using Bayesian maximum entropy (BME). The BME model performed well in terms of estimating short- (R2 = 0.74 and RMSE = 1.76 µg/m3) and long-term (R2 = 0.76 and RMSE = 1.3 µg/m3) exposure. Premature mortalities and economic losses were also assessed by applying localised concentration-response coefficients simulated in China. A total of 74,500 (95% confidence interval (CI): 23,900-124,500) and 538,400 (95% CI: 495,000-581,300) all-cause premature mortality cases were found to be associated with short- and long-term BC exposure, respectively. Meanwhile, short-term BC exposure was associated with economic losses ranging from 7.5 to 13.2 billion US dollars (USD) (1 USD = 6.36 RMB on January 19, 2022) based on amended human capital (AHC) and willingness to pay (WTP), accounting for 0.06%-0.1% of China's total gross domestic product (GDP) in 2017 (1.2 × 104 billion USD), respectively. The economic losses for long-term exposure varied from 53 to 93.2 billion USD based on AHC and WTP, accounting for 0.4%-0.8% of China's total GDP in 2017, respectively.

Differential Etv2 threshold requirement for endothelial and erythropoietic development.

Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages.

Assessment of the eco-toxicological effects in zoxamide polluted soil amended with fertilizers-An indoor evaluation.

Zoxamide is a benzamide fungicide applied to control diseases caused by oomycete fungi. Fertilizers are important agricultural supplies to adjust soil properties and increase nutrition. To investigate the impact of zoxamide and seven fertilizers urea, phosphate fertilizer, potash fertilizer, compound fertilizer, organic fertilizer, vermicompost and soya bean cakes on the soil environment, the enantioselective dissipation characteristics of zoxamide, soil enzyme activities, pH and N, P nutrition changes were comprehensively analyzed in our present study. The enantioseparation method was successfully validated to quantify the zoxamide enantiomers in soil by HPLC using Chiral NQ (2)-RH column. Our results demonstrated that the R-(-)- and S-(+)-zoxamide half dissipated in the range of 10.88-17.81 and 8.05-14.41 days, respectively. S-(+)-zoxamide disappeared faster in soil. The vermicompost accelerated the dissipation rate of S-(+)-zoxamide, while urea, phosphate, organic and vermicompost fertilizer increased the dissipation selectivity. Zoxamide and fertilizers other than urea caused soil acidification during 80 days. Zoxamide was beneficial to soil catalase, instead inhibited soil urease, dehydrogenase activities and available phosphorus content. No significant effects on sucrase activity and available nitrogen content were found by zoxamide. Vermicompost and soya bean cakes had lasting and outstanding performance in efficiently improving soil enzyme activity and N, P nutrition. The comprehensive understanding of the ecological impact induced by chiral pesticide enantiomers and fertilizers on soil is vital to ensure the sustainable development and safety of agricultural production.

Frontal Lobe Functions, Demoralization, Depression and Craving as Prognostic Factors and Positive Outcomes of Patients with Heroin Use Disorder Receiving 6 Months of Methadone Maintenance Treatment.

Methadone maintenance therapy (MMT) is a well-established and effective treatment for heroin use disorders. Whether frontal lobe function and demoralization serve as suitable prognostic and outcome assessment factors remains unknown. A quasi-experimental study was conducted with a single-group repeated-measures design at a medical center and mental hospital in Taiwan. We enrolled 70 participants (39 completed treatments and 31 dropped out). Frontal lobe function, demoralization, depression, and craving at three time points were analyzed. There were differences between patients who completed the treatment (n = 39) and those who did not (n = 31). Thirty-nine patients completed the treatment (average age, 45.5 years; 89.7% men; average duration of heroin use, 27.21 years; MMT, 38.18 mg/day). Post-MMT (6 months), frontal lobe function, demoralization, depression, and craving significantly improved. Dropouts had higher frontal lobe function, lower demoralization, higher craving, younger age, and earlier onset age than patients who completed the pretest treatment. Clinicians should be aware of the severity of demoralization. Clinicians may select suitable patients for MMT by assessing frontal lobe function, demoralization, craving, age, and onset age. A 6-month course of MMT improved demoralization, frontal lobe function, depression, and addiction. Six months of treatment was more effective than 3 months. Suitable patient identification and continuous treatment are important in MMT.