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In this study, we documented the impact of magnesium oxide nanoparticles (MgONPs) on the various morpho-physiological changes by root irrigation in tobacco plants in the matrix media, as well as the uptake and accumulation of the NPs over a range of concentrations (50–250 μg/mL). Our results showed that the seed germination rate was not affected following exposure to MgONPs for 5 days. Enhanced plant growth together with increased peroxidase activity (39.63 U mg−1 protein in the 250 μg/mL MgONPs treatment, 36.63 U mg−1 protein in the control), superoxide dismutase activity (30.15 U mg−1 protein compared to 26.95 U mg−1 protein in the control), and chlorophyll content (the chlorophyll a and b contents in 0 and 250 μg/mL of MgONPs were 0.21, 0.12 μg/g to 1.21, 0.67 μg/g, respectively) were observed after 30 days of MgONP treatment. However, the malondialdehyde, protein, and relative water contents did not differ significantly, indicating that the NPs in the test concentrations had no phytotoxicity and even promoted plant growth. Scanning electron microscopy and paraffin section observations indicated that the MgONPs did not affect the plant tissue structures and cells. In addition, an elevated Mg content was detected in the plant tissues exposed to MgONPs, suggesting that the Mg was taken up by the tobacco roots and translocated to the shoots and leaves, which were probably the most important tools to cause an increase in the chlorophyll content and stimulate growth. In particular, compared with the controls, a substantially higher Mg content was observed in the leaves (12.93 mg/g in the MgONPs treatment, 9.30 mg/g in the control) exposed to 250 μg/mL MgONPs, especially in the lower and middle leaves. This result confirmed that the contents of plant Mg-element in the old leaves were increased by MgONPs. In summary, this study investigated increased Mg uptake and growth stimulation, as well as the induction of various positive morpho-physiological changes to tobacco plants when exposed to MgONPs. Results elucidate the promotional impact of the NPs on plant health and their implications for agricultural safety and security.

Increased population movements and increased mobility made it possible for severe acute respiratory syndrome coronavirus 2, which is mainly spread by respiratory droplets, to spread faster and more easily. This study tracked and analysed the development of the coronavirus 2019 (COVID-19) outbreak in the top 100 cities that were destinations for people who left Wuhan before the city entered lockdown. Data were collected from the top 100 destination cities for people who travelled from Wuhan before the lockdown, the proportion of people travelling into each city, the intensity of intracity travel and the daily reports of COVID-19. The proportion of the population that travelled from Wuhan to each city from 10 January 2020 to 24 January 2020, was positively correlated with and had a significant linear relationship with the cumulative number of confirmed cases of COVID-19 in each city after 24 January (all P < 0.01). After the State Council launched a multidepartment joint prevention and control effort on 22 January 2020 and compared with data collected on 18 February, the average intracity travel intensity of the aforementioned 100 cities decreased by 60−70% (all P < 0.001). The average intensity of intracity travel on the nth day in these cities during the development of the outbreak was positively related to the growth rate of the number of confirmed COVID-19 cases on the n + 5th day in these cities and had a significant linear relationship (P < 0.01). Higher intensities of population movement were associated with a higher incidence of COVID-19 during the pandemic. Restrictions on population movement can effectively curb the development of an outbreak.

Background There remains a great need for effective therapies for cervical cancers, the majority of which are aggressive leaving patients with poor prognosis. Methods and results Here, we identify a novel candidate therapeutic target, trefoil factor 3 (TFF3) which overexpressed in cervical cancer cells and was associated with reduced postoperative survival. Functional studies demonstrated that TFF3 overexpression promoted the proliferation and invasion of cervical cancer cells, and inhibited the apoptosis by inducing the mRNA changes in SiHa and Hela cell lines. Conversely, TFF3 silencing disrupted the proliferation and invasion of cervical cancer cells, and induced the apoptosis via Click-iT EdU test, flow cytometry analysis and two-dimensional Matrigel Transwell analysis. Western blot analysis showed that overexpression of TFF3 repressed E-cadherin (CDH1) expression to promote the invasion of cervical cancer cells. Furthermore, down-regulated CDH1 via overexpression of TFF3 was significantly up-regulated by virtue of inhibitor of p-STAT3. Conclusions These results suggested that TFF3 stimulated the invasion of cervical cancer cells probably by activating the STAT3/CDH1 signaling pathway. Furthermore, overexpression of TFF3 decreased the sensitivity of cervical cancer cells to etoposide by increasing P-glycoprotein (P-gp) functional activity. Overall, our work provides a preclinical proof that TFF3 not only contributes to the malignant progression of cervical cancers and but also is a potential therapeutic target.

The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis, commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD pathophysiology involves environmental, genetic and metabolic factors, as well as changes in the intestinal microbiota and their products. Dysfunction of the intestinal barrier can contribute to NAFLD development and progression. Although there are technical limitations in assessing intestinal permeability in humans and the number of patients in these studies is rather small, fewer than half of the patients have increased intestinal permeability and translocation of bacterial products. Microbe-derived metabolites and the signalling pathways they affect might play more important roles in development of NAFLD. We review the microbial metabolites that contribute to the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. We discuss the mechanisms by which metabolites produced by microbes might affect disease progression and/or serve as therapeutic targets or biomarkers for NAFLD.

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease distributed globally in all ethnicities with increasing prevalence. If left untreated, the disease will lead to cirrhosis, liver failure, or death. The intestinal microbiota is a complex ecosystem located in the human intestine, which extensively affects the human physiological and pathological processes. With more and more in-depth understandings of intestinal microbiota, a substantial body of studies have verified that the intestinal microbiota plays a crucial role in a variety of digestive system diseases, including alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). However, only a few studies have paid attention to evaluate the relationship between AIH and the intestinal microbiota. While AIH pathogenesis is not fully elucidated yet, some studies have indicated that intestinal microbiota putatively made significant contributions to the occurrence and the development of AIH by triggering several specific signaling pathways, altering the metabolism of intestinal microbiota, as well as modulating the immune response in the intestine and liver. By collecting the latest related literatures, this review summarized the increasing trend of the aerobic bacteria abundance in both AIH patients and AIH mice models. Moreover, the combination of specific bacteria species was found distinct to AIH patients, which could be a promising tool for diagnosing AIH. In addition, there were alterations of luminal metabolites and immune responses, including decreased short-chain fatty acids (SCFAs), increased pathogen associated molecular patterns (PAMPs), imbalanced regulatory T (Treg)/Th17 cells, follicular regulatory T (TFR)/follicular helper T (TFH) cells, and activated natural killer T (NKT) cells. These alterations participate in the onset and the progression of AIH via multiple mechanisms. Therefore, some therapeutic methods based on restoration of intestinal microbiota composition, including probiotics and fecal microbiota transplantation (FMT), as well as targeted intestinal microbiota-associated signaling pathways, confer novel insights into the treatment for AIH patients.

Alcohol-associated liver disease (ALD) is one of the most common chronic liver diseases worldwide, contributing significantly to liver cirrhosis and hepatocellular carcinoma, with limited effective treatment options. Approximately 50% of patients with ALD exhibit iron overload, which can further trigger the occurrence of ferroptosis. Recent studies indicate that ferroptosis plays a role in the development and progression of ALD through pro-inflammatory and pro-fibrotic mechanisms. Additionally, the gut microbiota exerts a complex influence on ALD, with pathogens like Candida albicans and Enterococcus faecalis promoting its progression, whereas Bifidobacterium appears to have a protective effect. Emerging findings indicate that microorganisms like Lactobacillus and metabolites such as 1,3-diaminopropane and reuterin can modulate iron homeostasis. However, the intrinsic link between gut microbiota–derived metabolites and ferroptosis in ALD remains inconclusive. This review comprehensively synthesizes current knowledge regarding the microbiota–ferroptosis crosstalk in ALD, with particular emphasis on microbial regulation of hepatic iron homeostasis and microbiota-driven modulation of oxidative stress through lipid peroxidation and antioxidant system interactions. Notably, we propose either suppressing hepatic ferroptosis or inducing ferroptosis in pathogenic bacterial strains as dual therapeutic strategies to mitigate ALD progression. These insights highlight the therapeutic potential of the gut microbiota-ferroptosis axis, paving the way for precision management strategies in ALD. Graphical Abstract Gut microbiota-liver ferroptosis crosstalk in alcohol-associated liver disease (ALD). Alcohol consumption disrupts gut microbiota homeostasis, characterized by a reduction in beneficial bacteria and an increase in harmful bacteria, and enhances intestinal iron absorption. The resulting dysbiosis can further exacerbate iron uptake. Together, elevated iron levels and dysbiosis-induced oxidative stress and lipid peroxidation contribute to the induction of ferroptosis, thereby accelerating the progression of ALD. Targeting the gut microbiota–liver ferroptosis axis thus represents a promising therapeutic strategy for ALD. Abbreviations: FMT, fecal microbiota transplantation.

Background Impaired metabolic functions of gut microbiota have been demonstrated in alcohol-related liver disease (ALD), but little is known about changes in phenylalanine metabolism. Methods Bacterial genomics and fecal metabolomics analysis were used to recognize the changes of phenylalanine metabolism and its relationship with intestinal flora. Intestinal barrier function was detected by intestinal alkaline phosphatase (IAP) activity, levels of tight junction protein expression, colonic inflammation and levels of serum LPS. Lactobacillus acidophilus was chosen to correct phenylalanine metabolism of ALD mice by redundancy analysis and Pearson correlation analysis. Results Using 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods, we identified elevated levels of phenylalanine and its’ metabolites in the gut of alcohol-fed mice compared to control mice and were negatively correlated with the abundance of Lactobacillus , which mainly metabolized phenylalanine. The intestinal phenylalanine level was positively correlated with the colon inflammatory factors TNF-α and IL-6, and negatively correlated with ZO-1 and Occludin. While intestinal alkaline phosphatase (IAP) activity was negatively correlated with the colon inflammatory factors TNF-α, IL-6 and MCP-1, and positively correlated with ZO-1 and Occludin. Increased phenylalanine inhibited IAP activity, blocked LPS dephosphorylation, increased colonic inflammation and bacterial translocation. Phenylalanine supplementation aggravated alcohol-induced liver injury and intestinal barrier dysfunction. Among the 37 Lactobacillus species, the abundance of Lactobacillus acidophilus was most significantly decreased in ALD mice. Supplementation with L. acidophilus recovered phenylalanine metabolism and protected mice from alcohol-induced steatohepatitis. Conclusions Recovery of phenylalanine metabolism through the oral supplementation of L. acidophilus boosted intestinal barrier integrity and ameliorated experimental ALD.

Recently the roles of gut microbiota are highly regarded in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The intestinal bacteria regulate the metabolism of bile acids depending on bile salt hydrolase (BSH), 7-dehydroxylation, hydroxysteroid dehydrogenase (HSDH), or amide conjugation reaction, thus exerting effects on NAFLD development through bile acid receptors such as farnesoid X receptor (FXR), Takeda G-protein-coupled bile acid protein 5 (TGR5), and vitamin D receptor (VDR), which modulate nutrient metabolism and insulin sensitivity via interacting with downstream molecules. Reversely, the composition of gut microbiota is also affected by the level of bile acids in turn. We summarize the mutual regulation between the specific bacteria and bile acids in NAFLD and the latest clinical research based on microbiota and bile acids, which facilitate the development of novel treatment modalities in NAFLD.

Introduction To investigate the efficacy of a knowledge-based planning (KBP) model in optimizing dose distribution, and identify the inter-institutional variation in radiotherapy of recurrent nasopharyngeal carcinoma (rNPC). Methods A total of 70 rNPC patients treated with intensity-modulated radiotherapy (IMRT) were recruited to build a KBP model. Following model refinement, 36 patients were retrospectively enrolled for dosimetric comparison between manually optimized and KBP-generated plans. Ten experienced physicists from six different institutions were engaged to independently design manual plan for a representative case, to assess inter-institutional variations, and differences between KBP and manual plans. Results The refined KBP model provided significant reduced dose in brainstem D1cc (the dose received by the “hottest”1 cm3 volume, 41.14 ± 8.51 Gy vs 38.48 ± 8.60 Gy, P < 0.001) and spinal cord D1cc (17.48 ± 9.38Gy vs 12.23 ± 6.56Gy, P < 0.001). In addition, The mean dose (Dmean) of brainstem, spinal cord, mandible, parotid, temporomandibular joint and inner ear were statistically decreased (P < 0.05). In validation cohort, KBP model eliminated the hotspot (0.57 ± 0.01% vs 0.00 ± 0.00%, P < 0.001), improved target homogeneity (HI: 0.06 ± 0.00 vs 0.08 ± 0.00, P < 0.001), and performed superior to the manual plans in sparing organs. While all institutions achieved comparable target coverage, manual plans exhibited substantial variability in sparing brainstem. KBP implementation reduced inter-institutional dose disparities for brainstem (46.30 ± 10.08 Gy vs 41.80 ± 5.80 Gy, P = 0.041) and spinal cord (26.08 ± 7.06 Gy vs 18.19 ± 1.98 Gy, P = 0.002). Additionally, planning efficiency increased by 48.7% (39 vs 76 min). Conclusions This KBP framework optimized rNPC reirradiation from three dimensions: 1) Enhanced OARs’ protection; 2) Improved target homogeneity; 3) Improved the multi-institutional consistency and efficiency of planning. These advancements established a clinically actionable paradigm for precision reirradiation.

Cirrhosis and liver cancer caused by alcohol-associated liver disease (ALD) are serious threats to people's health. In addition to hepatic cell apoptosis and liver inflammation caused by oxidative stress during alcohol metabolism, intestinal microbiota disorders are also involved in the onset and development of ALD. Ethanol and its' oxidative and non-oxidative metabolites, together with dysbiosis-caused-inflammation, destroys the intestinal barrier. Changes of several microbial metabolites, such as bile acids, short-chain fatty acids, and amino acid, are closely associated with gut dysbiosis in ALD. The alcohol-caused dysbiosis can further influence intestinal barrier-related proteins, such as mucin2, bile acid-related receptors, and aryl hydrocarbon receptor (AhR), and these abnormal changes also participate in the injury of the intestinal barrier and hepatic steatosis. Gut-derived bacteria, fungi, and their toxins, such as lipopolysaccharide (LPS) and β-glucan translocate into the liver through the damaged intestinal barrier and promote the progression of inflammation and fibrosis of ALD. Thus, the prevention of alcohol-induced disruption of intestinal permeability has a beneficial effect on ALD. Currently, multiple therapeutic treatments have been applied to restore the gut microbiota of patients with ALD. Fecal microbial transplantation, probiotics, antibiotics, and many other elements has already shown their ability of restoring the gut microbiota. Targeted approaches, such as using bacteriophages to remove cytolytic Enterococcus faecalis , and supplement with Lactobacillus, Bifidobacterium , or boulardii are also powerful therapeutic options for ALD.