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The methanogenic degradation of oil hydrocarbons can proceed through syntrophic partnerships of hydrocarbon-degrading bacteria and methanogenic archaea 1 – 3 . However, recent culture-independent studies have suggested that the archaeon ‘ Candidatus Methanoliparum’ alone can combine the degradation of long-chain alkanes with methanogenesis 4 , 5 . Here we cultured Ca . Methanoliparum from a subsurface oil reservoir. Molecular analyses revealed that Ca . Methanoliparum contains and overexpresses genes encoding alkyl-coenzyme M reductases and methyl-coenzyme M reductases, the marker genes for archaeal multicarbon alkane and methane metabolism. Incubation experiments with different substrates and mass spectrometric detection of coenzyme-M-bound intermediates confirm that Ca . Methanoliparum thrives not only on a variety of long-chain alkanes, but also on n -alkylcyclohexanes and n -alkylbenzenes with long n -alkyl (C ≥13 ) moieties. By contrast, short-chain alkanes (such as ethane to octane) or aromatics with short alkyl chains (C ≤12 ) were not consumed. The wide distribution of Ca . Methanoliparum 4 – 6 in oil-rich environments indicates that this alkylotrophic methanogen may have a crucial role in the transformation of hydrocarbons into methane. ‘Candidatus Methanoliparum’ overexpresses genes encoding alkyl-coenzyme M and methyl-coenzyme M reductases—markers of archaeal multicarbon alkane and methane metabolism—and thrives on a variety of long-chain alkanes and n -alkylcyclohexanes, and n -alkylbenzenes with long n -alkyl (C ≥13 ) moieties.

Abiotic stresses, especially cold, salinity and drought, are the primary causes of crop loss worldwide. Plant adaptation to environmental stresses is dependent upon the activation of cascades of molecular networks involved in stress perception, signal transduction, and the expression of specific stress-related genes and metabolites. Plants have stress-specific adaptive responses as well as responses which protect the plants from more than one environmental stress. There are multiple stress perception and signaling pathways, some of which are specific, but others may cross-talk at various steps. In this review article, we first expound the general stress signal transduction pathways, and then highlight various aspects of biotic stresses signal transduction networks. On the genetic analysis, many cold induced pathways are activated to protect plants from deleterious effects of cold stress, but till date, most studied pathway is ICE-CBF-COR signaling pathway. The Salt-Overly-Sensitive (SOS) pathway, identified through isolation and study of the sos1, sos2, and sos3 mutants, is essential for maintaining favorable ion ratios in the cytoplasm and for tolerance of salt stress. Both ABA-dependent and -independent signaling pathways appear to be involved in osmotic stress tolerance. ROS play a dual role in the response of plants to abiotic stresses functioning as toxic by-products of stress metabolism, as well as important signal transduction molecules and the ROS signaling networks can control growth, development, and stress response. Finally, we talk about the common regulatory system and cross-talk among biotic stresses, with particular emphasis on the MAPK cascades and the cross-talk between ABA signaling and biotic signaling.

COVID-19 is still a global public health concern, and the SARS-CoV-2 mutations require more effective antiviral agents. In this study, the antiviral entry activity of thirty-one flavonoids was systematically evaluated by a SARS-CoV-2 pseudovirus model. Twenty-four flavonoids exhibited antiviral entry activity with IC50 values ranging from 10.27 to 172.63 µM and SI values ranging from 2.33 to 48.69. The structure–activity relationship of these flavonoids as SARS-CoV-2 entry inhibitors was comprehensively summarized. A subsequent biolayer interferometry assay indicated that flavonoids bind to viral spike RBD to block viral interaction with ACE2 receptor, and a molecular docking study also revealed that flavonols could bind to Pocket 3, the non-mutant regions of SARS-CoV-2 variants, suggesting that flavonols might be also active against virus variants. These natural flavonoids showed very low cytotoxic effects on human normal cell lines. Our findings suggested that natural flavonoids might be potential antiviral entry agents against SARS-CoV-2 via inactivating the viral spike. It is hoped that our study will provide some encouraging evidence for the use of natural flavonoids as disinfectants to prevent viral infections.

Scutellariae radix (“Huang-Qin” in Chinese) is a well-known traditional herbal medicine and popular dietary supplement in the world, extensively used in prescriptions of TCMs as adjuvant treatments for coronavirus pneumonia 2019 (COVID-19) patients in China. According to the differences in its appearance, Scutellariae radix can be classified into two kinds: ZiQin (1∼3 year-old Scutellariae baicalensis with hard roots) and KuQin (more than 3 year-old S. baicalensis with withered pithy roots). In accordance with the clinical theory of TCM, KuQin is superior to ZiQin in cooling down the heat in the lung. However, the potential active ingredients and underlying mechanisms of Scutellariae radix for the treatment of COVID-19 remain largely unexplored. It is still not clear whether there is a difference in the curative effect of ZiQin and KuQin for the treatment of COVID-19. In this research, network pharmacology, LC-MS based plant metabolomics, and in vitro bioassays were integrated to explore both the potential active components and mechanism of Scutellariae radix for the treatment of COVID-19. As the results, network pharmacology combined with molecular docking analysis indicated that Scutellariae radix primarily regulates the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin, and blocks SARS-CoV-2 spike binding to human ACE2 receptors. In vitro bioassays showed that baicalein and scutellarein exhibited more potent anti-inflammatory and anti-infectious effects than baicalin, the component with the highest content in Scutellariae radix . Moreover, baicalein inhibited SARS-CoV-2’s entry into Vero E6 cells with an IC 50 value of 142.50 μM in a plaque formation assay. Taken together, baicalein was considered to be the most crucial active component of Scutellariae radix for the treatment of COVID-19 by integrative analysis. In addition, our bioassay study revealed that KuQin outperforms ZiQin in the treatment of COVID-19. Meanwhile, plant metabolomics revealed that baicalein was the compound with the most significant increase in KuQin compared to ZiQin, implying the primary reason for the superiority of KuQin over ZiQin in the treatment of COVID-19.

Background This study aimed to observe the effect of transient receptor potential canonical channel 6 (TRPC6) antagonist 1-(β-[3-(4-method-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrate (SKF-96365) and its agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) on the proliferation of cervical cancer cell lines HeLa and SiHa, deoxyribonucleic acid (DNA) synthesis, cell migration, and TRPC6 expression. Method Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of TRPC6 in HeLa and SiHa cells. The tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the 5-ethynyl -2'- deoxyuridine (EdU) fluorescence detection assay, and a scratch test were used to detect the changes of proliferation, DNA synthesis and cell migration of HeLa and SiHa cells after SKF 96,365 and OAG acted on HeLa and SiHa cells for different lengths of time. RT-qPCR was used to detect expression changes of TRPC6 SKF-96365 and OAG treated HeLa and SiHa cells. Results TRPC6 was expressed both in HeLa and SiHa cells. The MTT assay showed that after 24 h of SKF-96365 treatment, compared with the control group, the proliferation of HeLa and SiHa cells was inhibited, and there was a statistically significant difference (p < 0.05). After 24 h of OAG, compared with the control group, the proliferation of HeLa and SiHa cells had increased, and there was a statistically significant difference (p < 0.05). EdU fluorescence detection showed that SKF-96365 could inhibit the DNA synthesis of HeLa and SiHa cells, and OAG could promote the DNA synthesis of HeLa and SiHa cells (p < 0.05) in HeLa and SiHa cell lines. Conclusion The high expression of calcium channel TRPC6 in HeLa and SiHa tissues may be related to the malignant behavior of cervical cancer cell lines HeLa and SiHa. This calcium channel may be a new target for the prevention and treatment of cervical cancer.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary. We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells. Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells. Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.

Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. Amomum kravanh is a traditional Chinese medicine used to relieve hangovers. However, whether its bioactive components improve alcohol metabolism is not clear. In this study, ten new (amomumols A-J, 1–10) and thirty-five known (11–45) compounds were isolated from the fruits of Amomum kravanh by an activity-guided separation. Ten novel compounds were identified as four sesquiterpenoids (1–4), three monoterpene derivatives (5–7), two neolignans (8, 9), and a novel norsesquiterpenoid (10) with a new C14 nor-bisabolane skeleton. Their structures were determined by the comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculation. The effects of all isolated compounds on the activity of alcohol dehydrogenase were evaluated in vitro, and it was found that eight compounds (11, 12, 15, 18, 26, and 36–38) exhibited significant activation effects on the alcohol dehydrogenase at 50 μM.

ObjectiveTo explore the effect of a single preoperative ultrasound-guided thoracic paravertebral nerve block (TPVB) and erector spinae plane block (ESPB) for perioperative analgesia in thoracoscopic pulmonary lobectomy.MethodsSeventy-two patients aged 40–70 years who underwent thoracoscopic pulmonary lobectomy under general anesthesia were enrolled and randomly divided into the control group (Group C), the TPVB group (Group T) and the ESPB group (Group E). The primary observation indicators included the visual analogue scale (VAS) at 1, 6, 12, 24, and 48 h postoperatively at rest and with a cough. The secondary observation indicators included the intraoperative sufentanil consumption, anesthesia awakening time and extubation time, the sufentanil consumption in the analgesic pump, and flurbiprofen ester consumption for remedial analgesia within 48 h after surgery and the incidence of postoperative adverse events.ResultsThe intraoperative sufentanil consumption, anesthesia awakening time, and extubation time were lower in groups T and E than those in group C (p < 0.05). Patients in group T had lower VAS scores at rest and with a cough at 1, 6, and 12 h postoperatively than in group C at the same time points (p < 0.05). The VAS scores at rest at 1 and 6 h postoperatively and coughing status at 1, 6, and 12 h postoperatively were lower in group E than in group C at the same time points (p < 0.05).ConclusionThe ultrasound-guided preoperative single TPVB and ESPB for thoracoscopic pulmonary lobectomy could both reduce the postoperative pain VAS score and reduce the dose of perioperative sufentanil and postoperative remedial analgesics.

5-fluorouracil (5-FU) is the most widely used anti-pyrimidine drug that exerts its cytotoxic effect by causing DNA damage. The Wnt/ -catenin pathway has been considered a promising strategy to improve chemosensitivity by enhancing the DNA damage response of chemotherapy drugs. Combination therapies against cancers could inevitably affect endogenous levels of ribonucleotides (RNs) and deoxyribonucleotides (dRNs) which are critical for DNA synthesis and repair. However, exploring satisfactory Wnt/ -catenin inhibitors for synergistic therapy through regulating RNs and dRNs remains challenging. Here, -derived carbon dots (A-CDs) with good bioactivity were synthesized via a one-step hydrothermal process, demonstrating both intrinsic Wnt/ -catenin inhibition and bioimaging capabilities to overcome the limitations of conventional Wnt/ -catenin inhibitors. The as-prepared A-CDs were further served as the transport vehicle for 5-FU, facilitating synergistic combination therapy by inhibiting the Wnt/ -catenin pathway, which could possibly accelerate nucleotide imbalance of dATP, ATP, TMP, and dUMP, ultimately leading to enhanced 5-FU efficiency. Additionally, the tumor-targeted material (HA-CDs@5-FU) was synthesized by modifying hyaluronic acid (HA) onto CDs@5-FU and exhibited superior antitumor efficacy in vivo with negligible side effects. Overall, this study provided a novel strategy for Wnt/ -catenin inhibition and synergistic therapy, providing insights into the application of nano-agents in cancer therapy.

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD’s binding with ACE2. Importantly, 6a and 6p (TC50 > 100 μM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p’s antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.