The Research Progress of Monogenic Inherited Hypertension

Monogenic inherited hypertension, which is caused by a single gene mutation, generally conforms to the Mendel’s law, but its phenotype is affected by environmental factors as well. This type of hypertension is characterized by early onset (more common in adolescents), family history, severe hypertension, or refractory hypertension. It is often accompanied by abnormal hormone level and biochemical indicators, including low activity of plasma renin, abnormal potassium, and acid-base metabolization disorder. For adolescents with a family history of moderate to severe hypertension, hormone level (including plasma renin-angiotensin-aldosterone, cortisol, and sex hormone) and blood electrolytes should be measured and the detailed diagnosis should be determined according to medical history, physical signs, and test results. Currently, 17 kinds of monogenic hereditary hypertension have been clearly determined. Thanks to the development of gene detection technology, the diagnostic level of monogenic inherited hypertension has greatly improved and the pathogenesis has been gradually clarified. Our review mainly discussed the research progress in this field

Automated Prompting for Non-overlapping Cross-domain Sequential Recommendation

Cross-domain Recommendation (CR) has been extensively studied in recent years to alleviate the data sparsity issue in recommender systems by utilizing different domain information. In this work, we focus on the more general Non-overlapping Cross-domain Sequential Recommendation (NCSR) scenario. NCSR is challenging because there are no overlapped entities (e.g., users and items) between domains, and there is only users' implicit feedback and no content information. Previous CR methods cannot solve NCSR well, since (1) they either need extra content to align domains or need explicit domain alignment constraints to reduce the domain discrepancy from domain-invariant features, (2) they pay more attention to users' explicit feedback (i.e., users' rating data) and cannot well capture their sequential interaction patterns, (3) they usually do a single-target cross-domain recommendation task and seldom investigate the dual-target ones. Considering the above challenges, we propose Prompt Learning-based Cross-domain Recommender (PLCR), an automated prompting-based recommendation framework for the NCSR task. Specifically, to address the challenge (1), PLCR resorts to learning domain-invariant and domain-specific representations via its prompt learning component, where the domain alignment constraint is discarded. For challenges (2) and (3), PLCR introduces a pre-trained sequence encoder to learn users' sequential interaction patterns, and conducts a dual-learning target with a separation constraint to enhance recommendations in both domains. Our empirical study on two sub-collections of Amazon demonstrates the advance of PLCR compared with some related SOTA methods

Protection of p-coumaric acid against chronic stress-induced neurobehavioral deficits in mice via activating the PKA-CREB-BDNF pathway

There is a body of evidence to suggest that chronic stress modulates neurochemical homeostasis, alters neuronal structure, inhibits neurogenesis and contributes to development of mental disorders. Chronic stress-associated mental disorders present common symptoms of cognitive impairment and depression with complex disease mechanisms. P-coumaric acid (p-CA), a natural phenolic compound, is widely distributed in vegetables, cereals and fruits. P-CA exhibits a wide range of health-related effects, including anti-oxidative-stress, anti-mutagenesis, anti-inflammation and anti-cancer activities. The current study aims to evaluate the therapeutic potential of p-CA against stress-associated mental disorders. We assessed the effect of p-CA on cognitive deficits and depression-like behavior in mice exposed to chronic restraint stress (CRS); we used network pharmacology, biochemical and molecular biological approaches to elucidate the underlying molecular mechanisms. CRS exposure caused memory impairments and depression-like behavior in mice; p-CA administration attenuated these CRS-induced memory deficits and depression-like behavior. Network pharmacology analysis demonstrated that p-CA was possibly involved in multiple targets and a variety of signaling pathways. Among them, the protein kinase A (PKA) - cAMP-response element binding protein (CREB) - brain derived neurotrophic factor (BDNF) signaling pathway was predominant and further characterized. The levels of PKA, phosphorylated CREB (pCREB) and BDNF were significantly lowered in the hippocampus of CRS mice, suggesting disruption of the PKA-CREB-BDNF signaling pathway signaling pathway; p-CA treatment restored the signaling pathway. Furthermore, CRS upregulated expression of proinflammatory cytokines in hippocampus, while p-CA reversed the CRS-induced effects. Our findings suggest that p-CA will offer therapeutic benefit to patients with stress-associated mental disorders

A weighted soil heath index approach for refined assessment of soil health in cropping systems

IntroductionPromoting sustainable crop production is enhanced by an effective method to assess soil health. However, soil health assessment is challenging due to multiple interactions among dynamic soil properties (i.e., soil health indicators) across management practices and agroecological regions. We tested several currently popular soil health assessment methods for cropping systems in Tennessee in the southeastern US and found that these methods failed to differentiate Tennessee soil health under long-term conservation and conventional management.Materials and methodsThis study developed a Tennessee weighted soil health index (WSHI) by: 1) selecting a set of management-sensitive soil health indicators, 2) assigning meaningful weights to indicators, and 3) normalizing the scores based on regionally relevant undisturbed natural reference sites. The tested cropping systems treatments were moldboard plow (MP) in continuous soybean (SS), no tillage (NT) in SS, NT with wheat cover (NTW) in SS, no cover and chisel plow (NCCT) in continuous cotton (CC), no cover and no tillage (NCNT) in CC, and hairy vetch cover and no tillage (VCNT) in CC. In addition, two woodlots and one grassland sites in the vicinity of the cropping systems were selected to represent undisturbed natural systems.Results and discussionOut of 22 indicators that proved to be management-sensitive, six were selected as a minimum dataset (MDS). These were particulate organic matter C (POM-C), soil respiration from 4-day incubation (4d CO2), small macroaggregate (0.250-2mm)-associated C (SMA-C), surface hardness (PR15), microbial biomass N (MBN), and bulk density (BD). Measured values of the MDS indicators were transformed into unitless normalized scores (based on the regional range of the indicator), and finally integrated into WSHI scores using a weighted-addition approach. Additionally, the soil health gap (SHG) between the soil health of the regional reference system and different cropping systems was calculated. Results revealed that WSHI strongly differentiated soil health between long-term conservation and conventional managements practices. The WSHI scores for southeastern cropland soils varied as follows: VCNT = NTW > NT > NCNT ≥ NCCT ≥ MP. The SHGs under MP, NCCT, NCNT, NT, NTW, and VCNT were 85.5, 79.9, 68, 45.1, 25.2, and 24.3, respectively, relative to the average WSHI of three undisturbed systems. Results showed that the WSHI approach is effective in more meaningful regional assessment of soil health and SHG can be a potential metric for comparing soil health across agroecological regions

Gene Expression Profiling of Lacrimal Glands Identifies the Ectopic Expression of MHC II on Glandular Cells as a Presymptomatic Feature in a Mouse Model of Primary Sjögren's Syndrome

Ectopic expression of MHC II molecules on glandular cells is a feature of primary Sjögren's syndrome (pSS). However, the cause of this ectopic expression and its potential role in the pathogenesis of the disease remains elusive. Here, we report that ectopic expression of MHC II molecules on glandular cells represents an early presymptomatic event in a mouse model of pSS induced by immunization of Ro60_316-335 peptide emulsified in TiterMax® as an adjuvant. Ectopic expression of MHC II was induced by TiterMax® but not by complete freund's adjuvant (CFA). Furthermore, immunization with Ro60_316-335 peptide emulsified in TiterMax®, but not in CFA, induced a pSS-like disease in mice. Our results suggests that ectopic expression of MHC II molecules on glandular cells represents a presymptomatic feature of pSS and that such ectopic expression can be induced by exogenous factors. In addition, this study also provides a novel mechanism how adjuvants can amplify immune responses

Pigments of aminophenoxazinones and viridomycins produced by termite-associated Streptomyces tanashiensis BYF-112

Termite-associated Streptomyces tanashiensis BYF-112 was found as a potential source for yellow and green pigments, which were stable under the tested temperature, light and metal ions. Eight metabolites (1–8), including four new natural yellow pigments aminophenoxazinones (1–4), and two rarely iron dependent green pigments viridomycin A and F (9–10) were isolated from BYF-112 cultured in YMS and YMS treated with FeSO4, respectively. The metabolites 2–4 displayed a significant safety performance on the normal liver cell line L-02, while the metabolite 1 showed weak cytotoxicity against the L-02 and several cancer cells. Especially, in the filter paper disc tests, the compound 1 possessed strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with the zone of inhibition (ZOI) of 15.3 mm, which was equal to that of referenced levofloxacin (ZOI = 15.2 mm). And the metabolite 1 also showed moderate antibacterial activities against Micrococcus teragenus and S. aureus, with the ZOI values of 15.3 and 17.2 mm. In addition, by the minimum inhibitory concentration (MIC) assay, the compound 1 displayed potential antibacterial activities against M. teragenus, S. aureus and MRSA, with the MIC values of 12.5, 12.5, and 25.0 μg/ml, respectively. The present results indicate that BYF-112 may be a promising source for safe and bioactive pigments, which can be used for further development and industrial applications

The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome

在这篇论文当中，郑俊峰博士领导的课题小组发现在人白细胞抗原二类基因（HLA-II）中，HLA-DRB1*0803是中国南方原发干燥综合征易感基因。进一步通过结构生物信息学模拟DRB1*0803 分子结构并分析，发现HLA的抗原肽结合槽口袋9的表面电势的不同，可能是疾病易感性差异的分子基础。自身免疫病是由遗传因素和环境因素共同导致的疾病，在遗传因素里，HLA位点是很多自身免疫病的主要易感基因。但是，尽管HLA和自身免疫病的相关性非常明确，这种相关背后的机理还不清楚。这项关于HLA和干燥综合征相关性的研究在这一问题上做出了探索性的发现，对HLA和干燥综合征的相关的机制提出了新的观点。该成果也是自身免疫学实验室在干燥综合征方向上陆续发表的第4篇学术论文。Primary Sjögren's syndrome (pSS) is associated with HLA-DRB1 loci, but the association of amino acid variations in the hypervariable region of the HLA-DR β1 chain with pSS is largely unknown. In this study, we aimed to identify the amino acid variations within the hypervariable region of HLA-DRB1 molecule which are associated with the susceptibility to pSS. We sequenced the 2nd exon of the HLA-DRB1 locus in 52 pSS patients and 179 controls. The HLA-DRB1*0803 is the allele that shows the strongest association with pSS in Chinese population (OR = 3.0, P = 2.4 × 10 −4 ). Furthermore, amino acid variations within the binding pocket P7 and P9 are associated with the susceptibility to pSS. An interaction between two residues within P7, β47 and β67, is associated with pSS. Structural modeling studies demonstrated that the electrostatics of peptide binding pocket 9 are opposite in pSS-susceptible and -protective HLA-DRB1 alleles. In conclusion, our results suggest that structural heterogeneity of the HLA-DRB1 peptide binding pocket P7 and P9 might play a role in the pathogenesis of pSS