Vertical patterns of chlorophyll a in the euphotic layer are related to mesoscale eddies in the South China Sea

Phytoplankton closely connects with the hydrodynamics and biogeochemical environment of the ocean. While research focusing on both the physiochemical factors and hydrodynamics regulating phytoplankton has already been conducted, the coupling mechanism between mesoscale eddies and the vertical distribution of phyto plankton in the South China Sea (SCS) is still not well understood. Here, phytoplankton was studied under one weak-cold and two warm eddies along the 18°N transect in the SCS. The results show that the vertical distribution of chlorophyll (chl-a) presented a similar pattern at all four sampling stations. The mixed layer is less than 50 m. It is the same as the meridional salinity gradients that may be distinguished above a depth of 60 m. The subsurface chlorophyll maximum at the edge of a warm (WI) and cold eddy (CI) at E413 and E411 was shallower than that at the edge of a warm eddy (WII) at E407 and E409, indicating that temperature and salinity may be the important driving factors. On the whole, mesoscale eddies had a significant influence on the vertical pattern of chl-a in the SCS during the study period

Secondary metabolites from the deep-sea derived fungus Aspergillus terreus MCCC M28183

Aspergillus fungi are renowned for producing a diverse range of natural products with promising biological activities. These include lovastatin, itaconic acid, terrin, and geodin, known for their cholesterol-regulating, anti-inflammatory, antitumor, and antibiotic properties. In our current study, we isolated three dimeric nitrophenyl trans-epoxyamides (1–3), along with fifteen known compounds (4–18), from the culture of Aspergillus terreus MCCC M28183, a deep-sea-derived fungus. The structures of compounds 1–3 were elucidated using a combination of NMR, MS, NMR calculation, and ECD calculation. Compound 1 exhibited moderate inhibitory activity against human gastric cancer cells MKN28, while compound 7 showed similar activity against MGC803 cells, with both showing IC50 values below 10 μM. Furthermore, compound 16 exhibited moderate potency against Vibrio parahaemolyticus ATCC 17802, with a minimum inhibitory concentration (MIC) value of 7.8 μg/mL. This promising research suggests potential avenues for developing new pharmaceuticals, particularly in targeting specific cancer cell lines and combating bacterial infections, leveraging the unique properties of these Aspergillus-derived compounds

TRPV1 Channel Contributes to the Behavioral Hypersensitivity in a Rat Model of Complex Regional Pain Syndrome Type 1

Complex regional pain syndrome type 1 (CRPS-I) is a debilitating pain condition that significantly affects life quality of patients. It remains a clinically challenging condition and the mechanisms of CRPS-I have not been fully elucidated. Here, we investigated the involvement of TRPV1, a non-selective cation channel important for integrating various painful stimuli, in an animal model of CRPS-I. A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. TRPV1 expression was significantly increased in hind paw tissue and small to medium-sized dorsal root ganglion (DRG) neurons of CPIP rats. CPIP rats showed increased TRPV1 current density and capsaicin responding rate in small-sized nociceptive DRG neurons. Local pharmacological blockage of TRPV1 with the specific antagonist AMG9810, at a dosage that does not produce hyperthermia or affect thermal perception or locomotor activity, effectively attenuated thermal and mechanical hypersensitivity in bilateral hind paws of CPIP rats and reduced the hyperexcitability of DRG neurons induced by CPIP. CPIP rats showed bilateral spinal astrocyte and microglia activations, which were significantly attenuated by AMG9810 treatment. These findings identified an important role of TRPV1 in mediating thermal and mechanical hypersensitivity in a CRPS-I animal model and further suggest local pharmacological blocking TRPV1 may represent an effective approach to ameliorate CRPS-I

Role of GABAAR in the Transition From Acute to Chronic Pain and the Analgesic Effect of Electroacupuncture on Hyperalgesic Priming Model Rats

Chronic pain is a costly health problem that impairs health-related quality of life when not effectively treated. Regulating the transition from acute to chronic pain is a new therapeutic strategy for chronic pain that presents a major clinical challenge. The underlying mechanisms of pain transition are not entirely understood, and strategies for preventing this transition are lacking. Here, a hyperalgesic priming model was used to study the potential mechanism by which γ-aminobutyric acid receptor type A (GABAAR) in the dorsal root ganglion (DRG) contributes to pain transition. Furthermore, electroacupuncture (EA), a modern method of acupuncture, was administered to regulate pain transition, and the mechanism underlying EA's regulatory effect was investigated. Hyperalgesic priming was induced by intraplanar injection of carrageenan (Car)/prostaglandin E2 (PGE2). The decrease in mechanical withdrawal threshold (MWT) induced by PGE2 returned to baseline 4 h after injection in NS + PGE2 group, and still persisted 24 h after injection in Car + PGE2 group. Lower expression of GABAAR in the lumbar DRG was observed in the model rats. Furthermore, activating or blocking GABAAR could reversed the long-lasting hyperalgesia induced by Car/PGE2 injection or produced a persistent hyperalgesia. In addition, GABAAR may be involved in Protein Kinase C epsilon (PKCε) activation in the DRG, a mark molecular of pain transition. EA considerably increased the mechanical pain thresholds of hyperalgesic priming model mammals in both the acute and chronic phases. Furthermore, EA upregulated the expression of GABAAR and inhibited the activation of PKCε in the DRG. In addition, peripheral administration of picrotoxin blocked the analgesic effect of EA on the model rats and abolished the regulatory effect of EA on PKCε activation. These findings suggested that GABAAR plays a key role in both the transition from acute to chronic pain and the analgesic effect of EA on hyperalgesic priming

Middle Holocene marine flooding and human response in the south Yangtze coastal plain, East China

Coastal flooding catastrophes have affected human societies on coastal plains around the world on several occasions in the past, and are threatening 21st century societies under global warming and sea-level rise. However, the role of coastal flooding in the interruption of the Neolithic Liangzhu culture in the lower Yangtze valley, East China coast has been long contested. In this study, we used a well-dated Neolithic site (the Yushan site) close to the present coastline to demonstrate a marine drowning event at the terminal stage of the Liangzhu culture and discuss its linkage to relative sea-level rise. We analysed sedimentology, chronology, organic elemental composition, diatoms and dinoflagellate cysts for several typical profiles at the Yushan site. The field and sedimentary data provided clear evidence of a palaeo-typhoon event that overwhelmed the Yushan site at ∼2560 BCE, which heralded a period of marine inundation and ecological deterioration at the site. We also infer an acceleration in sea-level rise at 2560–2440 BCE from the sedimentary records at Yushan, which explains the widespread signatures of coastal flooding across the south Yangtze coastal plain at that time. The timing of this mid-Holocene coastal flooding coincided with the sudden disappearance of the advanced and widespread Liangzhu culture along the lower Yangtze valley. We infer that extreme events and flooding accompanying accelerated sea-level rise were major causes of vulnerability for prehistoric coastal societies

Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study

Background: As effective medication to treat COVID-19 is currently unavailable, preventive remedies may be particularly important. Objective: To examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) level and COVID-19 infection, its severity, and its clinical case characteristics. Methods: This case-control study compared serum 25(OH)D levels and rates of vitamin D deficiency (VDD) between 80 healthy controls and 62 patients diagnosed with COVID-19 and admitted to Guangxi People’s Hospital, China, 2/16/2020–3/16/2020. Cases were categorized into asymptomatic, mild/moderate, and severe/critical disease. Logistic regression analysis was conducted to examine the associations between 25(OH)D level, or VDD, and case status/severity of COVID-19 while controlling for demographics and comorbidities. A threshold level of vitamin D for conveying COVID-19 risk was estimated. Results: Severe/critical COVID-19 cases were significantly older and had higher percentages of comorbidity (renal failure) compared to mild cases. The serum 25(OH)D concentration in COVID-19 patient was much lower than that in healthy control. And 25(OH)D level was the lowest in severe/ critical cases, compared with mild cases. In further, significantly higher rates of VDD were found in COVID-19 cases (41.9%) compared to healthy controls (11.1%). And VDD was the greatest in severe/critical cases (80%), compared with mild cases (36%). These statistically significant associations remained even after controlling for demographics and comorbidities. A potential threshold of 25(OH)D (41.19nmol/L) to protect against COVID-19 was identified. Conclusion: Elderly and people with comorbidities were susceptible to severe COVID-19 infection. VDD was a risk factor for COVID-19, especially for severe/critical cases. While further confirmation is needed, vitamin D supplementation may have prevention or treatment potential for COVID- 19 disease

Genomewide analysis of the lateral organ boundaries domain gene family in Eucalyptus grandis reveals members that differentially impact secondary growth

Lateral Organ Boundaries Domain (LBD) proteins are plant-specific transcription factors playing crucial roles in growth and development. However, the function of LBD proteins in Eucalyptus grandis remains largely unexplored. In this study, LBD genes in E. grandis were identified and characterized using bioinformatics approaches. Gene expression patterns in various tissues and the transcriptional responses of EgLBDs to exogenous hormones were determined by qRT-PCR. Functions of the selected EgLBDs were studied by ectopically overexpressing in a hybrid poplar (Populus alba 9 Populus glandulosa). Expression levels of genes in the transgenic plants were investigated by RNA-seq. Our results showed that there were forty-six EgLBD members in the E. grandis genome and three EgLBDs displayed xylem- (EgLBD29) or phloem-preferential expression (EgLBD22 and EgLBD37). Confocal microscopy indicated that EgLBD22, EgLBD29 and EgLBD37 were localized to the nucleus. Furthermore, we found that EgLBD22, EgLBD29 and EgLBD37 were responsive to the treatments of indol- 3-acetic acid and gibberellic acid. More importantly, we demonstrated EgLBDs exerted different influences on secondary growth. Namely, 35S::EgLBD37 led to significantly increased secondary xylem, 35S::EgLBD29 led to greatly increased phloem fibre production, and 35S:: EgLBD22 showed no obvious effects. We revealed that key genes related to gibberellin, ethylene and auxin signalling pathway as well as cell expansion were significantly up- or down-regulated in transgenic plants. Our new findings suggest that LBD genes in E. grandis play important roles in secondary growth. This provides new mechanisms to increase wood or fibre production.Figure S1 Conserved domains of EgLBD protein family.Figure S2 The chromosomal localization of the LBD gene family in Eucalyptus grandis.Figure S3 Subcellular localization of EgLBD22, EgLBD29 and EgLBD37 proteins.Figure S4 Gel electrophoresis analysis for the presence of the transgene in EgLBD22-oe, EgLBD29-oe and EgLBD37-oe plants.Figure S5 Validation for the expression of the transgene in EgLBD22-oe, EgLBD29-oe and EgLBD37-oe plants by qRT-PCR.Table S1 All the primers used in this study.Table S2 The coding sequences of LBD genes in Eucalyptus grandis.Table S3 The information of LBD gene family in Eucalyptus grandis.Table S4 Conserved motifs predicted by MEME program in EgLBD proteins.Table S5 Protein-protein interaction prediction for possible functional protein association networks of EgLBD22.Table S6 Protein-protein interaction prediction for possible functional protein association networks of EgLBD29.Table S7 Protein-protein interaction prediction for possible functional protein association networks of EgLBD37.Table S8 The differentially expressed genes between EgLBD22-oe and WT-84k plants.Table S9 The differentially expressed genes between EgLBD29-oe and WT-84k plants.Table S10 The differentially expressed genes between EgLBD37-oe and WT-84k plants.Table S11 The information of eight key differentially expressed genes in EgLBD22-oe, EgLBD29-oe and EgLBD37-oe plants.Basic Research Fund of RIF [RIF2014-01]; Natural Science Foundation of China [31670676]; Mondi and Sappi through the Forest Molecular Genetics Programme; Technology and Human Resources for Industry Programme [UID 80118]; National Research Foundation of South Africa [UID 18312, 71255, 86936]http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1467-7652am2018Forestry and Agricultural Biotechnology Institute (FABI)Genetic

Targeting Neddylation and Sumoylation in Chemoresistant Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC

Electroacupuncture Regulates Pain Transition Through Inhibiting PKCε and TRPV1 Expression in Dorsal Root Ganglion

Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4-L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε-TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system

Specificity for the correlation between the body surface and viscera in the pathological state of COPD: A prospective, controlled, and assessor-blinded trial

Background: The association between the body surface and viscera remains obscure, but a better understanding of the body surface-viscera correlation will maximize its diagnostic and therapeutic values in clinical practice. Therefore, this study aimed to investigate the specificity of body surface-viscera correlation in the pathological state.Methods: The study subjects included 40 participants with chronic obstructive pulmonary disease (COPD) in the COPD group and 40 age-matched healthy participants in the healthy control group. Laser Doppler flowmetry, infrared thermography, and functional near-infrared spectroscopy were respectively adopted to measure 1) the perfusion unit (PU), 2) temperature, and 3) regional oxygen saturation (rSO2) of four specific sites distributed in the heart and lung meridians. These three outcome measures reflected the microcirculatory, thermal, and metabolic characteristics, respectively.Results: Regarding the microcirculatory and thermal characteristics of the body surface, the PU and temperature of specific sites on the body surface [i.e., Taiyuan (LU9) and Chize (LU5) in the lung meridian] in the COPD group were significantly increased compared with healthy controls (p < 0.05), whereas PU and temperature of other sites in the heart meridian [i.e., Shenmen (HT7) and Shaohai (HT3)] did not change significantly (p > 0.05). Regarding the metabolic characteristics, rSO2 of specific sites in the lung meridian [i.e., Taiyuan (LU9) and Chize (LU5)] and Shaohai (HT3) of the heart meridian in the COPD group was significantly decreased compared with healthy controls (p < 0.01), whereas rSO2 of Shenmen (HT7) in the heart meridian did not change significantly (p > 0.05).Conclusion: In the disease state of COPD, the microcirculatory, thermal, and metabolic characteristics of specific sites on the body surface in the lung meridian generally manifest more significant changes than those in the heart meridian, thereby supporting relative specificity for the body surface-viscera correlation in the pathological state