Buffer zone-based trace elements indicating the impact of human activities on karst urban groundwater.

The tanglesome allocation of landscape types at various spatial dimensions is an important component influencing the quality of groundwater environment in karst cities. Trace elements can be used as indicators of the extent of impact on groundwater which is an effective means of tracing groundwater contamination. In this study, we studied the influence of landscape patterns on trace elements in groundwater of typical karst cities in Southwest China (Guiyang City) on a multi-spatial scale by using multivariate statistical analysis. According to the sampling points, buffer zone scales with different radii (500 m, 1000 m, 1500 m, and 4000 m) were established to quantify the land use model. There are suburban and urban differences in trace element content. The city center has higher levels of trace elements compared to suburban areas, especially Li, Ni, Tl, Cu, Sr, Co, As, and Mn. In addition, the outcomes of the multiple linear regression had shown that the size effect of the association from landscape pattern to trace elements varies with different indicators and parameters. The results of redundancy analysis showed an overall change in trace elements was better interpreted by the landscape pattern of the 1500 m-scale buffer. At the same time, at the 1500 m scale, Ni, Tl, Cu, Co, As, Cr, Sr, Li, and Mn were positively correlated with the urban landscape index (4LPI, 4LSI), influenced by urban anthropogenic activities, while Cd, Zn, and Pb were positively correlated with the cropland landscape index (1AI, 1LPI), influenced by agricultural activities. This study indicates that trace elements are a reliable indicator for tracing groundwater contamination. The buffer zone can reflect the extent of urban impacts on groundwater and provide a new and effective analytical tool for groundwater management.

PET Imaging of Lung Cancers in Precision Medicine: Current Landscape and Future Perspective.

Despite the recent advances in cancer treatment, lung cancer remains the leading cause of cancer mortality worldwide. Immunotherapies using immune checkpoint inhibitors (ICIs) achieved substantial efficacy in nonsmall cell lung cancer (NSCLC). Currently, most ICIs are still a monoclonal antibody (mAb). Using mAbs or antibody derivatives labeled with radionuclide as the tracers, immunopositron emission tomography (immunoPET) possesses multiple advantages over traditional 18F-FDG PET in imaging lung cancers. ImmunoPET presents excellent potential in detecting, diagnosing, staging, risk stratification, treatment guidance, and recurrence monitoring of lung cancers. By using radiolabeled mAbs, immunoPET can visualize the biodistribution and uptake of ICIs, providing a noninvasive modality for patient stratification and response evaluation. Some novel targets and associated tracers for immunoPET have been discovered and investigated. This Review introduces the value of immunoPET in imaging lung cancers by summarizing both preclinical and clinical evidence. We also emphasize the value of immunoPET in optimizing immunotherapy in NSCLC. Lastly, immunoPET probes developed for imaging small cell lung cancer (SCLC) will also be discussed. Although the major focus is to summarize the immunoPET tracers for lung cancers, we also highlighted several small-molecule PET tracers to give readers a balanced view of the development status.

Clinical Efficacy of Bevacizumab Plus XELOX Chemotherapy in Colorectal Cancer and Application Value of Mindfulness-Based Stress Reduction Intervention.

Background and Objectives: Colorectal cancer (CRC) is a malignant tumor with an extremely high incidence rate worldwide. This study explores the influence of mindfulness-based stress reduction (MBSR) in the care of patients with CRC undergoing bevacizumab (BVZ) plus XELOX chemotherapy, aiming at providing reliable reference and guidance for further improving their rehabilitation and prognosis. Methods: Between January 2019 and March 2020, 88 patients with CRC admitted consecutively to Jiangsu Cancer Hospital in China were enrolled in the study. Of them, 42 patients receiving BVZ plus XELOX chemotherapy, conventional care and MBSR intervention were assigned to the intervention group, and the remaining 46 patients receiving XELOX chemotherapy and conventional care were included in the control group. Clinical efficacy, safety and improvement in functional status were compared. Patients' psychological state, treatment compliance and self-care ability were evaluated. Finally, prognostic quality of life (QoL) was recorded at 1-year follow-up. Results: The overall response rate and incidence of adverse events in the intervention group were not different in the control group, but the total control rate and improvement rate in the intervention group were higher. After treatment, Sedation-Agitation Scale (SAS) and Self-Rating Depression Scale (SDS) scores in the intervention group were decreased, compliance and self-care ability were improved, all of which were better than in the control group. Prognostic follow-up showed that the QoL in the intervention group was also higher than in the control group. Conclusions: The combined use of BVZ in XELOX-based chemotherapy can improve the clinical outcome and functional status of patients with CRC. In addition, MBSR intervention implemented during chemotherapy can effectively optimize patients' psychological state and treatment compliance, strengthen their self-care ability and improve their prognostic QoL.

Clinical and genetic risk factors for radiation-associated ototoxicity: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

BACKGROUND: Cranial radiation therapy (CRT) is associated with ototoxicity, which manifests as hearing loss and tinnitus. The authors sought to identify clinical determinants and genetic risk factors for ototoxicity among adult survivors of pediatric cancer treated with CRT. METHODS: Logistic regression evaluated associations of tinnitus (n = 1991) and hearing loss (n = 2198) with nongenetic risk factors and comorbidities among CRT-treated survivors in the Childhood Cancer Survivor Study. Genome-wide association studies (GWASs) of CRT-related tinnitus and hearing loss were also performed. RESULTS: Males were more likely to report CRT-related tinnitus (9.4% vs 5.4%; P = 5.1 × 10-4 ) and hearing loss (14.0% vs 10.7%; P = .02) than females. Survivors with tinnitus or hearing loss were more likely to experience persistent dizziness or vertigo (tinnitus: P < 2 × 10-16 ; hearing loss: P = 6.4 × 10-9 ), take antidepressants (tinnitus: P = .02; hearing loss: P = .01), and report poorer overall health (tinnitus: P = 1.5 × 10-6 ; hearing loss: P = 1.7 × 10-6 ) in comparison with controls. GWAS of CRT-related tinnitus revealed a genome-wide significant signal in chromosome 1 led by rs203248 (P = 1.5 × 10-9 ), whereas GWAS of CRT-related hearing loss identified rs332013 (P = 5.8 × 10-7 ) in chromosome 8 and rs67522722 (P = 7.8 × 10-7 ) in chromosome 6 as nearly genome-wide significant. A replication analysis identified rs67522722, intronic to ATXN1, as being significantly associated with CRT-related hearing loss (P = .03) and de novo hearing loss (P = 3.6 × 10-4 ). CONCLUSIONS: CRT-associated ototoxicity was associated with sex, several neuro-otological symptoms, increased antidepressant use, and poorer self-reported health. GWAS of CRT-related hearing loss identified rs67522722, which was supported in an independent cohort of survivors. LAY SUMMARY: Hearing loss and subjective tinnitus (the perception of noise or ringing in the ear) are long-term side effects of cancer treatment and are common in children treated with radiation to the brain. These toxicities can affect childhood development and potentially contribute to serious learning and behavioral difficulties. This study's data indicate that males are at greater risk for hearing loss and tinnitus than females after radiation therapy to the brain. Those who develop these toxicities are more likely to use antidepressants and report poorer overall health. Health care providers can improve the management of survivors by informing patients and/or their parents of these risks.

Zhengganxifeng Decoction Affects Gut Microbiota and Reduces Blood Pressure via Renin-Angiotensin System.

Zhengganxifeng decoction (ZGXFD) is a traditional Chinese medicinal formula, from "Medical Zhong parameter West recorded" by Xichun Zhang, which has been applied to the treatment of clinical essential hypertension. Besides its effect in blood pressure reduction, ZGXFD is also known to be a radical therapy with little or no side effects. Compared with western medicines, Chinese medicinal formulas have the advantage of simultaneously attacking multiple targets. However, such a property brings trouble to the pharmacological studies of Chinese medicines. This study investigated the composition of gut microbiota in spontaneously hypertensive rats (SHR) treated with ZGXFD. ZGXFD was shown to cause similar effects in the treatment group as benazepril: both were able to reduce in SHR the microbial diversity, Firmicutes to Bacteroidetes (F/B) ratio and coccus to bacillus (C/B) ratio. Meanwhile, ZGXFD can maintain the integrity of intestinal mechanistic barrier and elevate the percentage of bacteria producing short chain fatty acids (SCFA). By investigating renin-angiotensin system (RAS) system, we found that ZGXFD can decrease the expression of angiotensin-converting-enzyme (ACE) in lungs, which in turn causes a increase in AngI produces angiotensin1-7 (Ang1-7) and decrease in AngII. ZGXFD regulate blood pressure in SHR via RAS.

Biochemical characterization, structure-guided mutagenesis, and application of a recombinant D-allulose 3-epimerase from Christensenellaceae bacterium for the biocatalytic production of D-allulose.

D-Allulose has become a promising alternative sweetener due to its unique properties of low caloric content, moderate sweetness, and physiological effects. D-Allulose 3-epimerase (DAEase) is a promising enzyme for D-Allulose production. However, the low catalytic efficiency limited its large-scale industrial applications. To obtain a more effective biocatalyst, a putative DAEase from Christensenellaceae bacterium (CbDAE) was identified and characterized. The recombinant CbDAE exhibited optimum activity at pH 7.5°C and 55°C, retaining more than 60% relative activity from 40°C to 70°C, and the catalytic activity could be significantly increased by Co2+ supplementation. These enzymatic properties of purified CbDAE were compared with other DAEases. CbDAE was also found to possess desirable thermal stability at 55°C with a half-life of 12.4 h. CbDAE performed the highest relative activity towards D-allulose and strong affinity for D-fructose but relatively low catalytic efficiency towards D-fructose. Based on the structure-guided design, the best double-mutation variant G36N/W112E was obtained which reached up to 4.21-fold enhancement of catalytic activity compared with wild-type (WT) CbDAE. The catalytic production of G36N/W112E with 500 g/L D-fructose was at a medium to a higher level among the DAEases in 3.5 h, reducing 40% catalytic reaction time compared to the WT CbDAE. In addition, the G36N/W112E variant was also applied in honey and apple juice for D-allulose conversion. Our research offers an extra biocatalyst for D-allulose production, and the comprehensive report of this enzyme makes it potentially interesting for industrial applications and will aid the development of industrial biocatalysts for D-allulose.

Recent trends in extraction, purification, structural characterization, and biological activities evaluation of Perilla frutescens (L.) Britton polysaccharide.

Perilla frutescens (L.) Britton is an annual herb plant of the Perilla genus in the Labiatae family, which is commonly utilized as an edible and medicinal resource. Polysaccharides are among the major components and essential bioactive compounds of P. frutescens, which exhibit a multitude of biological activities, including antioxidant, antitumor, anti-fatigue, immunoregulation, hepatoprotective, anti-inflammatory, and lipid-lowering effects. As a natural carbohydrate, P. frutescens polysaccharide has the potential to be utilized in the development of drugs and functional materials. In this paper, we provide an overview of progress made on the extraction, purification, structural characterization, and bioactivity of polysaccharides from different parts of P. frutescens. The challenges and opportunities for research are discussed, along with the potential development prospects and future areas of focus in the study of P. frutescens polysaccharides.

A review of the extraction and purification methods, biological activities, and applications of active compounds in Acanthopanax senticosus.

Acanthopanax senticosus (AS) is a geo-authentic crude medicinal plant that grows in China, Korea, Russia, and Japan. AS contains bioactive compounds such as eleutherosides, polysaccharides, and flavonoids. It is also a key traditional herb in the Red List of Chinese Species. AS is mainly distributed in Northeast China, specifically in Heilongjiang, Jilin, and Liaoning provinces. Its active compounds contribute to significant biological activities, including neuroprotective, antioxidant, anti-fatigue, and antitumor effects. However, the extraction methods of active compounds are complex, the extraction efficiency is poor, and the structure-activity relationship is unclear. This study focused on the nutrients in AS, including protein, carbohydrates, and lipids. Particularly, the active ingredients (eleutherosides, polysaccharides, and flavonoids) in AS and their extraction and purification methods were analyzed and summarized. The biological activities of extracts have been reviewed, and the mechanisms of anti-oxidation, antitumor, anti-inflammation, and other activities are introduced in detail. The applications of AS in various domains, such as health foods, medicines, and animal dietary supplements, are then reported. Compared with other extraction methods, ultrasonic or microwave extraction improves efficiency, yet they can damage structures. Challenges arise in the recovery of solvents and in achieving extraction efficiency when using green solvents, such as deep eutectic solvents. Improvements can be made by combining extraction methods and controlling conditions (power, temperature, and time). Bioactive molecules and related activities are exposited clearly. The applications of AS have not been widely popularized, and the corresponding functions require further development.

A regional comparative study on the mismatch between population urbanization and land urbanization in China.

By taking 31 provinces (municipalities/autonomous regions) in Mainland China as the object of research, and using the data on urban population and built-up area of each region from 2005 to 2019, this paper measures the dispersion coefficient of population urbanization and land urbanization in each region through models and visually expresses the level and type of imbalance between them to reveal the temporal and spatial characteristics of imbalance. The results of the research show that since China's state-owned land was sold through bidding, auction, and listing, the overall urbanization of the population and land development have become unbalanced. There is obvious regional and category difference in imbalance between population urbanization and land urbanization. The degree of imbalance increases from the central, eastern, northeastern to western regions. The remaining 29 regions are generally lagging in population urbanization except for Beijing and Hebei province. This imbalance is mainly caused by China's dual household registration system, dual land system and the asymmetrical tax distribution system between financial rights and administrative rights.

Comprehensive association analysis of speech recognition thresholds after cisplatin-based chemotherapy in survivors of adult-onset cancer.

PURPOSE: Deficits in speech understanding constitute one of the most severe consequences of hearing loss. Here we investigate the clinical and genetic risk factors for symmetric deterioration of speech recognition thresholds (SRT) among cancer survivors treated with cisplatin. METHODS: SRT was measured using spondaic words and calculating the mean of measurements for both ears with symmetric SRT values. For clinical associations, SRT-based hearing disability (SHD) was defined as SRT≥15 dB hearing loss and clinical variables were derived from the study dataset. Genotyped blood samples were used for GWAS with rank-based inverse normal transformed SRT values as the response variable. Age was used as a covariate in association analyses. RESULTS: SHD was inversely associated with self-reported health (p = 0.004). Current smoking (p = 0.002), years of smoking (p = 0.02), BMI (p < 0.001), and peripheral motor neuropathy (p = 0.003) were positively associated with SHD, while physical activity was inversely associated with SHD (p = 0.005). In contrast, cumulative cisplatin dose, peripheral sensory neuropathy, hypertension, and hypercholesterolemia were not associated with SHD. Although no genetic variants had an association p value < 5 × 10-8 , 22 genetic variants were suggestively associated (p < 10-5 ) with SRT deterioration. Three of the top variants in 10 respective linkage disequilibrium regions were either positioned within the coding sequence or were eQTLs for genes involved in neuronal development (ATE1, ENAH, and ZFHX3). CONCLUSION: Current results improve our understanding of risk factors for SRT deterioration in cancer survivors. Higher BMI, lower physical activity, and smoking are associated with SHD. Larger samples would allow for expansion of the current findings on the genetic architecture of SRT.

Application of three-dimensional (3D) reconstruction in the treatment of video-assisted thoracoscopic complex segmentectomy of the lower lung lobe: A retrospective study.

Background: An increasing number of lung ground-glass nodules (GGNs) have been detected ever since low-dose computer tomography started growing in popularity. Three-dimensional (3D) reconstruction technology plays a critical role in lung resection, especially in segmentectomy. In this study, we explore the role of 3D reconstruction in thoracoscopic complex segmentectomy of lower lung lobe. Methods: A total of 97 patients who underwent complex segmentectomy of lower lung lobe from January 2021 to March 2022 were retrospectively analyzed. We divided these patients into a 3D group (n = 42) and a routine group (n = 55) based on preoperative 3D reconstruction or without this procedure. The demographics of patients and GGNs were collected and perioperative outcomes were compared between the two groups. Results: All of the baseline characteristics between the groups were comparable (all P > 0.05). There was no 30-day postoperative mortality and conversion in the two groups. The operation time of the 3D group was significantly shorter than that of the routine group (111.4 ± 20.8 min vs. 127.1 ± 32.3 min, P = 0.007). The number of stapler reloads during surgery in the 3D group was less than that in the routine group (9.0 ± 2.2 vs. 10.4 ± 2.6, P = 0.009). The rate of air leakage on postoperative days 1-3 was lower in the 3D group (11.9% vs. 30.9%, P = 0.027). In addition, the resection margins of all patients in the 3D group were adequate, while four patients in the routine group had inadequate resection margins, although there was no statistically significant difference (P = 0.131). Intraoperative blood loss, postoperative drainage, postoperative hospital stay, pneumonia/atelectasis, and hemoptysis were similar between the two groups. Conclusions: For performing complex segmentectomy of the lower lung lobe, the procedure of 3D reconstruction may shorten the operation time, decrease the number of stapler reloads, prevent postoperative air leakage, and guarantee a safe surgical margin. Therefore, 3D reconstruction is recommended for complex segmentectomy of the lower lung lobe.

Preparation, Physicochemical Characterization, and Antioxidant Activity of Naringin-Silk Fibroin-Alginate Microspheres and Application in Yogurt.

Naringin is the major polyphenol in bitter orange peel with antioxidant property. However, its pH sensitivity, low solubility, and bitter taste limit its application in food. In this study, naringin-sodium alginate-silk fibroin microspheres were prepared by the ionic gel method. The loading capacity and encapsulation efficiency of naringin in microspheres were 13.2% and 77.6%, respectively. The morphology of microspheres was characterized by scanning electron microscopy. The X-ray diffractometry and differential scanning calorimetry results showed naringin was amorphous after encapsulation. Fourier-transform infrared spectroscopy and molecular docking analysis confirmed the intermolecular hydrogen bonds between naringin and sodium alginate. Naringin could release from the microspheres continuously under different pH conditions. Compared with free naringin, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and the stability of naringin microspheres were significantly improved. The application of naringin microspheres in yogurt indicated the precipitation of whey could be effectively reduced and the decline rate of pH was inhibited. The study suggested that naringin encapsulated microspheres were beneficial for improving the shelf life of this bioactive product as well as providing a new idea for functional yogurt.

Confinement-Enhanced Selective Oxidation of Lignin Derivatives to Formic Acid Over Fe-Cu/ZSM-5 Catalysts Under Mild Conditions.

Aqueous-phase oxidation by H2 O2 , known as the Fenton-type process, provides an attractive route to convert recalcitrant lignin derivatives to valuable chemicals under mild conditions. The development of this technology is, however, limited by the uncontrolled selectivity, resulting from the highly reactive nature of H2 O2 and the thermodynamically favored deep oxidation to form CO2 . This study demonstrated that formic acid could be produced with a high selectivity (up to 80.3 % at 313 K) from the Fenton-type oxidation of guaiacol and several other lignin derivatives over a bimetallic Fe-Cu catalyst supported on a ZSM-5 zeolite. Combined experimental and theoretical investigations unveiled that the micropores of the zeolite support, which contained active metal sites, preferred to adsorb C2 -C4 intermediates over formic acid because of its stronger dispersive interaction with the larger guest molecules. This confinement effect significantly suppressed the secondary oxidation of formic acid, accounting for the uniquely high formic acid selectivity over Fe-Cu/ZSM-5.

Altered centromedial amygdala functional connectivity in adults is associated with childhood emotional abuse and predicts levels of depression and anxiety.

BACKGROUND: Childhood maltreatment is significantly associated with greater occurrence of mental disorders in adulthood such as depression and anxiety. As a key node of the limbic system, the amygdala is engaged in emotional processing and regulation and is dysfunctional in many psychiatric disorders. The present study aimed at exploring the association between childhood maltreatment and amygdala-based functional networks and their potential contributions to depression and anxiety. METHODS: Totally 90 Chinese healthy volunteers participated in a resting-state fMRI experiment. Levels of childhood maltreatment experience were assessed using the Childhood Trauma Questionnaire (CTQ-SF) as well as levels of depression and anxiety. Associations between CTQ-SF scores and bilateral amygdala gray matter volume and resting-state functional connectivity (RSFC) of the amygdala and selected regions of interest were analyzed using multiple regression analyses with sex and age as covariates. A subsequent moderation analysis was performed to identify whether associations were predictive of depression and anxiety levels. RESULTS: Childhood maltreatment was significantly negatively associated with RSFC between left amygdala and anterior insula. Further sub-region analyses revealed that this negative association only occurred for the left centromedial amygdala subregion, which subsequently moderated the relationship between levels of childhood emotional abuse and depression / anxiety. LIMITATIONS: No psychiatric patients were involved and specific neural associations with different childhood maltreatment subtypes need to be examined in future studies. CONCLUSION: The present findings provide evidence for altered RSFC of centromedial amygdala and the anterior insula associated with childhood maltreatment and which moderate levels of depression and anxiety in adulthood.

The Rostral Ventromedial and Lateral Medulla Are the Major Areas Responsive to Lung Cancer Progression among Brainstem Lung-Innervating Nuclei.

In recent years, the information crosstalk between the central nervous system and the periphery has been a hot topic, such as the brain-gut axis, brain-lung axis, etc. Among them, some studies have shown that brainstem nuclei activity can significantly affect the progression of peripheral tumor; however, regarding lung cancer, our understanding of the basic characteristics of the lung-innervating brain nuclei responsive to lung cancer progression remains deficient. Therefore, we used the pseudorabies virus for retrograde labeling of nerves to study the neural circuits between the lung and brain. We then established a mouse orthotopic lung cancer model and used the expression of the c-Fos gene in brain regions to characterize activated brain circuits and compared these results with those of the control group. We focused on c-Fos activity in nuclei associated with retrograde tracing regions of the brainstem. We found over 16 nuclei in the whole brain with direct or indirect lung innervation through neural retrograde labeling with the pseudorabies virus. We further revealed that the neuronal activity of the rostral ventrolateral reticular nucleus (RVL), caudal nucleus of Raphe (raphe obscurus nucleus, ROb), Raphe pallidus nucleus (RPa), and ventral gigantocellular reticular nucleus (GiV) in the rostral ventromedial and lateral medulla were significantly changed in an orthotopic lung cancer mouse model by the immunostaining of c-Fos early responsive protein. Thus, the distinctive rostroventral medulla area, functionally closely related to the vagus nerve, likely plays a role in central neural interaction with peripheral lung tumors and deserves future investigation.

Integrative pan-cancer analysis and clinical characterization of the N7-methylguanosine (m7G) RNA modification regulators in human cancers.

Background: RNA modification is one of the epigenetic mechanisms that regulates post-transcriptional gene expression, and abnormal RNA modifications have been reported to play important roles in tumorigenesis. N7-methylguanosine (m7G) is an essential modification at the 5' cap of human mRNA. However, a systematic and pan-cancer analysis of the clinical relevance of m7G related regulatory genes is still lacking. Methods: We used univariate Cox model and Kaplan-Meier analysis to generate the forest plot of OS, PFI, DSS and identified the correlation between the altered expression of m7G regulators and patient survival in 33 cancer types from the TCGA and GTEx databases. Then, the "estimate" R-package, ssGSEA and CIBERSORT were used to depict the pan-cancer immune landscape. Through Spearman's correlation test, we analyzed the correlation between m7G regulators and the tumor microenvironment (TME), immune subtype, and drug sensitivity of the tumors, which was further validated in NSCLC. We also assessed the changes in the expression of m7G related regulatory genes in NSCLC with regards to the genetic and transcriptional aspects and evaluated the correlation of METTL1 and WDR4 expression with TMB, MSI and immunotherapy in pan-cancer. Results: High expression of most of the m7G regulators was significantly associated with worse prognosis. Correlation analyses revealed that the expression of majority of the m7G regulators was correlated with tumor immune infiltration and tumor stem cell scores. Drug sensitivity analysis showed that the expression of CYFP1,2 was closely related to drug sensitivity for various anticancer agents (p < 0.001). Analysis of the pan-cancer immune subtype revealed significant differences in the expression of m7G regulators between different immune subtypes (p < 0.001). Additionally, the types and proportions of mutations in METTL1 and WDR4 and their relevance to immunotherapy were further described. Conclusion: Our study is the first to evaluate the correlation between the altered expression of m7G regulators and patient survival, the degree of immune infiltration, TME and drug sensitivity in pan-cancer datasets.

Discovery of hit compounds for methyl-lysine reader proteins from a target class DNA-encoded library.

Methyl-lysine (Kme) reader domains are prevalent in chromatin regulatory proteins which bind post-translational modification sites to recruit repressive and activating factors; therefore, these proteins play crucial roles in cellular signaling and epigenetic regulation. Proteins that contain Kme domains are implicated in various diseases, including cancer, making them attractive therapeutic targets for drug and chemical probe discovery. Herein, we report on expanding the utility of a previously reported, Kme-focused DNA-encoded library (DEL), UNCDEL003, as a screening tool for hit discovery through the specific targeting of Kme reader proteins. As an efficient method for library generation, focused DELs are designed based on structural and functional features of a specific class of proteins with the intent of novel hit discovery. To broadly assess the applicability of our library, UNCDEL003 was screened against five diverse Kme reader protein domains (53BP1 TTD, KDM7B JmjC-PHD, CDYL2 CD, CBX2 CD, and LEDGF PWWP) with varying structures and functions. From these screening efforts, we identified hit compounds which contain unique chemical scaffolds distinct from previously reported ligands. The selected hit compounds were synthesized off-DNA and confirmed using primary and secondary assays and assessed for binding selectivity. Hit compounds from these efforts can serve as starting points for additional development and optimization into chemical probes to aid in further understanding the functionality of these therapeutically relevant proteins.

Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.

PURPOSE: Cisplatin is a critical component of first-line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin-induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy. METHODS: Utilizing linear and logistic regression analyses on 1680 well-characterized cisplatin-treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities. Genome-wide association studies and gene-based analyses were performed on each phenotype. RESULTS: Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self-reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork-related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10-6 ) in gene-based analysis. rs62283056 in WFS1 previously found to be significantly associated with hearing loss (n = 511), was marginally significant in an independent replication cohort (p = 0.06; n = 606). Gene-based analyses identified significant associations between tinnitus and WNT8A (p = 2.5 × 10-6 ), encoding a signaling protein important in germ cell tumors. CONCLUSIONS: Genetics variants in TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies.

Home Garden With Eco-Healing Functions Benefiting Mental Health and Biodiversity During and After the COVID-19 Pandemic: A Scoping Review.

The COVID-19 pandemic has led to tremendous impacts on human lives and society, which are not only because of negative effects on people's mental health due to isolation policies and physical distance for mitigating the spread of SARS-CoV-2, but also because the incident post-acute sequelae of the coronavirus will cause mental disorders. A green environment is a health resource, which cannot only benefit human physical and mental health, but also increases biodiversity, contributes to flood mitigation, and cools urban areas. A home garden, as a kind of small green space, can provide ecosystem services with eco-healing functions in reducing mental stress during the isolation period of the COVID-19 pandemic through the garden itself and physical activities in it. Such an eco-healing approach within a mini-therapeutic landscape can also benefit biodiversity by enhancing plant diversity in residence and increasing biodiversity at a large scale. In this article, we propose a conceptual framework describing a home garden as "ecological medicine" with healing functions to improve mental health, as well as indirectly enhancing urban biodiversity. A home garden, as a mini-type of green landscape with biodiversity content, allows people to get close with nature so that it can promote comfortable and natural feelings during the pandemic. Furthermore, such an eco-healing home garden approach benefiting urban biodiversity can meet the challenges in maintaining environmental and mental health in post COVID-19 pandemic recovery, as well as preparing unknown next-surge risks with potential isolation regulations.

Waterscapes for Promoting Mental Health in the General Population.

The WHO estimates that, with the development of urbanization, 25% of the population is suffering from psychological and mental distress. Preliminary evidence has suggested that aquatic environments and riparian areas, i.e., waterscapes, can benefit psychological and mental wellbeing. The aim of this study was to identify the processes of waterscape psychological and mental health promotion through aliterature review. We propose a design framework of waterscapes for achieving psychological and mental health in the general population that often visits waterscapes, which has the function of therapeutic landscapes through values of accessibility, versatility, habitats, and biodiversity. According to theories, waterscapes can improve psychological and mental health to divert negative emotions through mitigation (e.g., reduced urban heat island), instoration (e.g., physical activity and state of nature connectedness), and restoration (e.g., reduced anxiety/attentional fatigue). By accessing water (e.g., streams, rivers, lakes, wetlands, and the coast) and riparian areas, people can get in close contact with nature and spend more time in activities (e.g., walking, exploring, talking, and relaxing). Waterscapes with healing effects can enhance psychological resilience to promote people's psychological and mental health. Future research should focus on ensuring an adequate supply of waterscapes and promoting the efficiency of waterscape ecosystem services on mental health. Moreover, fora deep understanding of the complexity of nature-human health associations, it is necessary to explore more consistent evidence for therapeutic waterscapes considering the characteristics and functional mechanisms of waterscape quality, in terms of freshness, luminescence, rippling or fluidity, and cultural value, to benefit public health and biodiversity conservation.