Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.

BACKGROUND: Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored. MAIN BODY: Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed. CONCLUSION: OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.

Increased Plasma Homocysteine Levels Are Associated with Left Ventricular Hypertrophy in Hypertensive Patients with Normal Renal Function.

INTRODUCTION: Renal function has an important bearing on plasma homocysteine levels. Plasma homocysteine is related to left ventricular hypertrophy (LVH). However, it remains unclear whether the association between plasma homocysteine levels and LVH is influenced by renal function. This study aimed to investigate relationships among left ventricular mass index (LVMI), plasma homocysteine levels, and renal function in a population from southern China. METHODS: A cross-sectional study was performed in 2,464 patients from June 2016 to July 2021. Patients were divided into three groups based on gender-specific tertiles of homocysteine levels. LVMI ≥115 g/m2 for man or ≥95 g/m2 for woman was defined as LVH. RESULTS: LVMI and the percentage of LVH were increased, while estimated glomerular filtration rate (eGFR) was decreased with the increase in homocysteine levels, both significantly. Multivariate stepwise regression analysis showed that eGFR and homocysteine were independently associated with LVMI in patients with hypertension. No correlation was observed between homocysteine and LVMI in patients without hypertension. Stratified by eGFR, further analysis confirmed homocysteine was independently associated with LVMI (ß = 0.126, t = 4.333, p < 0.001) only in hypertensive patients with eGFR ≥90 mL/(min·1.73 m2), not with 60≤ eGFR <90 mL/(min·1.73 m2). Multivariate logistic regression indicated that in hypertensive patients with eGFR ≥90 mL/(min·1.73 m2), the patients in high tertile of homocysteine levels had a nearly twofold increased risk of occurring LVH compared with those in low tertile (high tertile: OR = 2.780, 95% CI: 1.945-3.975, p < 0.001). CONCLUSION: Plasma homocysteine levels were independently associated with LVMI in hypertensive patients with normal eGFR.

CsMYB1 integrates the regulation of trichome development and catechins biosynthesis in tea plant domestication.

Tea trichomes synthesize numerous specialized metabolites to protect plants from environmental stresses and contribute to tea flavours, but little is known about the regulation of trichome development. Here, we showed that CsMYB1 is involved in the regulation of trichome formation and galloylated cis-catechins biosynthesis in tea plants. The variations in CsMYB1 expression levels are closely correlated with trichome indexes and galloylated cis-catechins contents in tea plant populations. Genome resequencing showed that CsMYB1 may be selected in modern tea cultivars, since a 192-bp insertion in CsMYB1 promoter was found exclusively in modern tea cultivars but not in the glabrous wild tea Camellia taliensis. Several enhancers in the 192-bp insertion increased CsMYB1 transcription in modern tea cultivars that coincided with their higher galloylated cis-catechins contents and trichome indexes. Biochemical analyses and transgenic data showed that CsMYB1 interacted with CsGL3 and CsWD40 and formed a MYB-bHLH-WD40 (MBW) transcriptional complex to activate the trichome regulator genes CsGL2 and CsCPC, and the galloylated cis-catechins biosynthesis genes anthocyanidin reductase and serine carboxypeptidase-like 1A. CsMYB1 integratively regulated trichome formation and galloylated cis-catechins biosynthesis. Results suggest that CsMYB1, trichome and galloylated cis-catechins are coincidently selected during tea domestication by harsh environments for improved adaption and by breeders for better tea flavours.

Selection or education? Medical school ranking and medical students' speciality choice preferences in the United States.

Limited research exists on the influence of top-ranked medical schools on students' speciality choice. We surveyed medical students (n = 468) at eight medical schools in the United States including two ranked in the top 10. Significance tests and logistic regressions were used to determine the relationship between school ranking and preferences for various speciality attributes. An analysis was conducted separately for students in lower (1st and 2nd) years versus higher (3rd and 4th) years of medical school. Among students in lower years, speciality preferences by students in top-ranked schools were less likely to be influenced by the length of training or work-life balance compared to students in non-top-ranked schools. Among higher year students, speciality preference of students in top-ranked schools was more likely to be influenced by prestige than their peers, with no difference in the influence of other factors. We also found evidence that students in top-ranked schools were less likely to be interested in primary care specialities, and this was more pronounced among those in higher years. Our findings suggest that top-ranked schools may influence speciality choice through both selection and education, and initiatives aimed at changing the emphasis on speciality prestige at top-ranked schools could increase primary care physician output.

[Design and implementation of real-time control of changes to national Chinese medicine resources fill system based on GIS].

The dynamic monitoring data of traditional Chinese medicine resources is one of the important tasks of the dynamic monitoring system of Chinese medicine resources,the system has formed a periodic monitoring data reporting mechanism. Data authenticity and accuracy are the basis for the sustainable and healthy development of Chinese medicine resources dynamic monitoring,information technology is an effective means to improve the efficiency of data reporting, reporting quality. Data production based on dynamic monitoring is of great significance for grasp the trend of change and development of Chinese medicine resources. In order to achieve the real-time control of changes to the national Chinese medicine resources, we build the Chinese medicine resources dynamic monitoring system. In order to solve the problems in practice, we have upgraded the fill system by using the data of GIS. In order to achieve the multidimensional, improve safety, practicality and standardization of the data, which laid a foundation for subsequent processing of data. The system can collect the information of the cultivation of Chinese herbal medicines,production and sales of daily reporting data, provide the Chinese herbal medicine market,fast growing industry environment such as positioning center. In this paper, the design and implementation of the system are expounded.According to the business requirements, we designed 12 forms, 98 collection indicators to meet the needs of dynamic monitoring of traditional Chinese medicine resources. This paper will introduce the development content, design and implementation, main function characteristics and application effect of the national Chinese medicine resources fill System. To explain the role that GIS technology plays in the system and how to realize the cultivation of Chinese herbal medicines, production and sales of daily reporting data, provide the Chinese herbal medicine market,fast growing industry environment such as positioning center,and information collecting.

Variations of stomata development in tea plant (Camellia sinensis) leaves in different light and temperature environments and genetic backgrounds.

Stomata perform important functions in plant photosynthesis, respiration, gas exchange, and interactions with environments. However, tea plant stomata development and functions are not known. Here, we show morphological changes during stomata development and genetic dissection of stomata lineage genes regulating stomata formation in tea developing leaves. Different tea plant cultivars displayed clear variations in the stomata development rate, density and size, which are closely related to their tolerance against dehydration capabilities. Whole sets of stomata lineage genes were identified to display predicted functions in regulating stomatal development and formation. The stomata development and lineage genes were tightly regulated by light intensities and high or low temperature stresses, which affected stomata density and function. Furthermore, lower stomatal density and larger size were observed in triploid tea varieties as compared to those in diploid plant. Key stomata lineage genes such as CsSPCHs, CsSCRM, and CsFAMA showed much lower expression levels, whereas negative regulators CsEPF1 and CsYODAs had higher expression levels in triploid than in diploid tea varieties. Our study provides new insight into tea plant stomatal morphological development and the genetic regulatory mechanisms on stomata development under abiotic stresses and genetic backgrounds. The study lays a foundation for future exploring of the genetic improvement of water use efficiency in tea plants for living up to the challenge of global climate change.

Barnacle-Inspired Wet Tissue Adhesive Hydrogels with Inherent Antibacterial Properties for Infected Wound Treatment.

Currently, antibiotics are the most common treatment for bacterial infections in clinical practice. However, with the abuse of antibiotics and the emergence of drug-resistant bacteria, the use of antibiotics has faced an unprecedented challenge. It is imminent to develop nonantibiotic antimicrobial agents. Based on the cation-π structure of barnacle cement protein, a polyphosphazene-based polymer poly[(N,N-dimethylethylenediamine)-g-(N,N,N,N-dimethylaminoethyl p-ammonium bromide (ammonium bromide)-g-(N,N,N,N-dimethylaminoethyl acetate ethylammonium bromide)] (PZBA) with potential adhesion and inherent antibacterial properties was synthesized, and a series of injectable antibacterial adhesive hydrogels (PZBA-PVA) were prepared by cross-linking with poly(vinyl alcohol) (PVA). PZBA-PVA hydrogels showed good biocompatibility, and the antibacterial rate of the best-performed hydrogel reached 99.81 ± 0.04% and 98.80 ± 2.16% against Staphylococcus aureus and Escherichia coli within 0.5 h in vitro, respectively. In the infected wound model, the healing rate of the PZBA-PVA-treated group was significantly higher than that of the Tegaderm film group due to the fact that the hydrogel suppressed inflammatory responses and modulated the infiltration of immune cells. Moreover, the wound healing mechanism of the PZBA-PVA hydrogel was further evaluated by real-time polymerase chain reaction and total RNA sequencing. The results indicated that the process of hemostasis and tissue development was prompted and the inflammatory and immune responses were suppressed to accelerate wound healing. Overall, the PZBA-PVA hydrogel is shown to have the potential for infected wound healing application.

SnS-quantum dot solar cells using novel TiC counter electrode and organic redox couples.

Low-cost quantum-dot sensitized solar cells (QDSSCs) were fabricated by using the earth-abundant element SnS quantum dot, novel TiC counter electrodes, and the organic disulfide/thiolate (T(2)/T(-)) redox couple, and reached an efficiency of 1.03 %. QDSSCs based on I(-)/I(3)(-), T(2)/T(-), and S(2-)/S(x)(2-) redox couples were assembled to study the role of the redox couples in the regeneration of sensitizers. Charge-extraction results reveal the reasons for the difference in J(SC) in three QDSSCs based on I(-)/I(3)(-), T(2)/T(-), and S(2-)/S(x)(2-) redox couples. The catalytic selectivity of TiC and Pt towards T(2)/T(-) and I(-)/I(3)(-) redox couples was investigated using Tafel polarization and electrochemical impedance analysis. These results indicated that Pt and TiC show a similar catalytic selectivity for I(-)/I(3)(-). However, TiC possesses better catalytic activity for T(2)/T(-) than for I(-)/I(3)(-). These results indicate the great potential of transition metal carbide materials and organic redox couples used in QDSSCs.

Metabolite Profiling and Transcriptome Analysis Revealed the Conserved Transcriptional Regulation Mechanism of Caffeine Biosynthesis in Tea and Coffee Plants.

Caffeine is a characteristic bioactive compound in tea and coffee plants, which is synthesized and accumulated extensively in leaves and seeds. However, little is known about the regulatory mechanism of caffeine synthesis in plants. This study compared the caffeine metabolite between tea and coffee plants. We found that tea leaves contained significantly higher caffeine than coffee leaves, which is perhaps due to more members of N-methyltransferase (NMT) genes as well as higher expression levels in tea plants. Substantial numbers of transcription factors were predicted to be involved in caffeine biosynthesis regulation, combining weighted gene co-expression network analysis and the cis-element of NMT promoter analysis in tea and coffee plants. Furthermore, analysis of the transcription factors from the caffeine-related modules suggested that the regulatory mechanism of caffeine biosynthesis was probably partly conservative in tea and coffee plants. This study provides an essential resource for the regulatory mechanism of caffeine biosynthesis in plants.

Integrating metabolite and transcriptome analysis revealed the different mechanisms of characteristic compound biosynthesis and transcriptional regulation in tea flowers.

The flowers of tea plants (Camellia sinensis), as well as tea leaves, contain abundant secondary metabolites and are big potential resources for the extraction of bioactive compounds or preparation of functional foods. However, little is known about the biosynthesis and transcriptional regulation mechanisms of those metabolites in tea flowers, such as terpenoid, flavonol, catechins, caffeine, and theanine. This study finely integrated target and nontarget metabolism analyses to explore the metabolic feature of developing tea flowers. Tea flowers accumulated more abundant terpenoid compounds than young leaves. The transcriptome data of developing flowers and leaves showed that a higher expression level of later genes of terpenoid biosynthesis pathway, such as Terpene synthases gene family, in tea flowers was the candidate reason of the more abundant terpenoid compounds than in tea leaves. Differently, even though flavonol and catechin profiling between tea flowers and leaves was similar, the gene family members of flavonoid biosynthesis were selectively expressed by tea flowers and tea leaves. Transcriptome and phylogenetic analyses indicated that the regulatory mechanism of flavonol biosynthesis was perhaps different between tea flowers and leaves. However, the regulatory mechanism of catechin biosynthesis was perhaps similar between tea flowers and leaves. This study not only provides a global vision of metabolism and transcriptome in tea flowers but also uncovered the different mechanisms of biosynthesis and transcriptional regulation of those important compounds.

The association of two polymorphisms in adiponectin-encoding gene with hypertension risk and the changes of circulating adiponectin and blood pressure: A meta-analysis.

OBJECTIVES: This meta-analysis was prepared to synthesize published data on the association of two polymorphisms (T45G and G276T) in adiponectin-encoding gene (ADIPOQ) with hypertension risk and the changes of circulating adiponectin and blood pressure. Methodology and Major Findings: Data were collected and corrected by two authors, and were managed with Stata software. In total, 12 articles were synthesized, including 12 studies (3358 cases and 5121 controls) for the association of two study polymorphisms with hypertension risk and 11 studies (3053 subjects) for the between-genotype changes of adiponectin and/or blood pressure. Based on all qualified studies, the risk prediction for hypertension was nonsignificant for both polymorphisms, with significant heterogeneity for G276T polymorphism (I2 = 53.8%). Overall changes in adiponectin and blood pressure were also nonsignificant for T45G, while contrastingly 276GT genotype was associated with significantly higher levels of adiponectin (weighted mean difference [WMD] = 0.72 µg/mL, 95% confidence interval [CI]: 0.04 to 1.41, P = 0.038), systolic (WMD = 5.15 mm Hg, 95% CI: 0.98 to 9.32, P = 0.016) and diastolic (WMD = 3.45 mm Hg, 95% CI: 0.37 to 6.53, P = 0.028) blood pressure with evident heterogeneity (I2 = 72.0%, 78.3% and 80.0%, respectively), and these associations were more obvious in hypertensive patients. Publication bias was a low probability event for overall comparisons. CONCLUSIONS: Our findings suggested that in spite of the nonsignificant association between ADIPOQ T45G or G276T polymorphism and hypertension, the heterozygous mutation of G276T was observed to account for increased levels of circulating adiponectin and blood pressure, especially in hypertensive patients.

A Promising Recombinant Herpesvirus of Turkeys Vaccine Expressing PmpD-N of Chlamydia psittaci Based on Elongation Factor-1 Alpha Promoter.

The obligate intracellular Gram-negative bacterium Chlamydia psittaci often causes avian chlamydiosis and influenza-like symptoms in humans. However, the commercial subunit C. psittaci vaccine could only provide a partial protection against avian chlamydiosis due to poor cellular immune response. In our previous study, a recombinant herpesvirus of turkeys (HVT)-delivered vaccine against C. psittaci and Marek's disease based on human cytomegalovirus (CMV) promoter (rHVT-CMV-pmpD) was developed and provided an effective protection against C. psittaci disease with less lesions and reduced chlamydial loads. In this study, we developed another recombinant HVT vaccine expressing the N-terminal fragment of PmpD (PmpD-N) based on human elongation factor-1 alpha (EF-1α) promoter (rHVT-EF-pmpD) by modifying the HVT genome within a bacterial artificial chromosome. The related characterization of rHVT-EF-pmpD was evaluated in vitro in comparison with that of rHVT-CMV-pmpD. The expression of PmpD-N was determined by western blot. Under immunofluorescence microscopy, PmpD-N protein of both two recombinant viruses was located in the cytoplasm and on the cell surface. Growth kinetics of rHVT-EF-pmpD was comparable to that of rHVT-CMV-pmpD, and the growth rate of rHVT-EF-pmpD was apparently higher than that of rHVT-CMV-pmpD on 48, 72, and 120 h postinfection. Macrophages activated by rHVT-EF-pmpD could produce more nitric oxide and IL-6 than that activated by rHVT-CMV-pmpD. In this study, a recombinant HVT vaccine expressing PmpD-N based on EF-1α promoter was constructed successfully, and a further research in vivo was needed to analyze the vaccine efficacy.

8-hydroxy-dipropylaminotetralin promotes neural plasticity in epileptic rats with depression.

Rats with chronic pilocarpine-induced temporal lobe epilepsy complicated with depression were studied. Anti-5-bromodeoxyuridine immunofluorescence staining and Timms staining showed that neurogenesis within the hippocampal dentate gyrus and mossy fiber sprouting were increased in model rats. Neurogenesis within the hippocampal dentate gyrus was further enhanced, while mossy fiber sprouting was decreased in model rats administered carbamazepine alone or in combination with the 5-hydroxytryptamine 1A receptor agonist, 8-hydroxy-dipropylaminotetralin (0.1 and 1 mg/kg). Among the groups, the effect was the most significant in rats receiving carbamazepine in conjunction with 1 mg/kg 8-hydroxy-dipropylaminotetralin. Thus, high dose 8-hydroxy-dipropylaminotetralin can improve neural plasticity in epileptic rats with depression.

Highly efficient inorganic-organic heterojunction solar cells based on SnS-sensitized spherical TiO2 electrodes.

All-solid-state inorganic-organic heterojunction solar cells (HSCs) were designed and fabricated using earth-abundant element, non-toxic, low-cost SnS-sensitized mesoporous spherical TiO(2) films under ambient conditions using a solution-processable, simple, and convenient fabrication technique. SnS-HSCs show a promising photovoltaic performance, with an efficiency of 2.8% and a significantly high V(OC) of 0.85 V.