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Fisch. is a medicinal plant commonly cultivated in salinized soils, where environmental stress suppresses the accumulation of pharmaceutically active components. To date, only limited studies have examined whether , a root endophytic fungus with growth-promoting and stress-alleviating properties, can improve the salt tolerance and medicinal quality of , particularly at the physiological and transcriptional levels. In this study, we successfully established a symbiotic system between and . To evaluate responses to salt stress, -inoculated and non-inoculated plants were subjected to NaCl treatments at 0, 100, 200, 300, and 350 mM, with 18 biological replicates per treatment. Colonization by was confirmed through microscopic examination and molecular identification. Growth phenotypes, antioxidant enzyme activities, membrane lipid peroxidation levels, chlorophyll-related indices, and the accumulation of key medicinal components were systema4tically quantified in symbiotic across different growth stages. Inoculation with significantly increased plant height, root length, and dry weight by 27.8%, 25.5%, and 52.2%, respectively. The symbiotic association enhanced the activities of the antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD) by 48.4% and 27.5%, respectively. Although malondialdehyde (MDA) content initially increased by 16.5% due to early fungal colonization, the canopy SPAD value simultaneously increased by 20.3%. These findings suggest that colonization is associated with differential oxidative stress responses between roots and shoots. Furthermore, under the high salt concentration of 300 mM NaCl, the contents of liquiritin and glycyrrhizic acid were markedly increased by 124.7% and 62.5%, respectively. enhanced the accumulation of secondary metabolites by modulating key rate-limiting enzyme genes rather than indiscriminately activating entire metabolic pathways. For example, the symbiont significantly upregulated in triterpenoid saponin biosynthesis and in flavonoid biosynthesis. These transcriptional changes may contribute to alleviating salt-induced constraints on secondary metabolite accumulation. In conclusion, colonization significantly improved growth performance, stress resistance, and medicinal compound accumulation in under salt stress. This study provides a theoretical foundation for improving the cultivation quality of in saline soils.

BackgroundGastric intestinal metaplasia (GIM) is a precancerous lesion associated with dysplasia and gastric cancer (GC). Annually, 1.8%, 10% and 73% of patients with atrophic gastritis, GIM and dysplasia progress to GC. While dyspepsia is associated with Helicobacter Pylori and active gastritis, GIM is not thought to be associated with specific symptoms. The aim of the study is to evaluate the correlation between GIM and pre-endoscopy symptoms.Methods2874 participants underwent 7480 gastroscopies with updated Sydney System gastric mucosal sampling from January 2004 – December 2010 with GIM graded using the Operative Link in Gastric Intestinal Metaplasia (OLGIM) staging. Prior to each endoscopy, the participants completed a medical history interview reporting symptoms of dyspepsia, acid brash, heartburn, dysphagia, nausea, vomiting, early satiety, indigestion, loss of weight, loss of appetite, coffee ground vomitus and melena. Results were compiled and statistics calculated using R for chi-square and logistic regression analysis.ResultsGIM was present in 53.3% (n=3992) of the gastroscopies. One-third of the patients (37.1%, n=2781) were symptomatic prior to the endoscopy, with the most common symptoms being dyspepsia (n=1860, 24.9%), acid brash (n=838, 11.2%) and heartburn (n=520, 7%).Compared to controls, patients with GIM have lower proportions of symptoms (34.2% vs 39.8%, p<0.01). Of note, patients with GIM reported significantly less acid brash (9.5% vs 12.7%, p<0.01) and heartburn (5.2% vs 8.5%, p<0.01) (IDDF2022-ABS-0213 Table1), whereby H. pylori status was not significantly different in these subgroups.Abstract IDDF2022-ABS-0213 Table 1Symptoms in patients with or without GIM Symptoms No GIM (%) GIM (%) Total (%) P-value Odds ratio (CI) Acid brash No 3484 (87.3) 3158 (90.5) 6642 (88.8) <0.001 0.72 (0.62–0.83) Yes 508 (12.7) 330 (9.5) 838 (11.2) Heartburn No 3653 (91.5) 3307 (94.8) 6960 (93.0) <0.001 0.59 (0.49 - 0.71) Yes 339 (8.5) 181 (5.2) 520 (7.0) Dysphagia No 3939 (98.7) 3462 (99.3) 7401 (98.9) 0.019 0.56 (0.35 - 0.89) Yes 53 (1.3) 26 (0.7) 79 (1.1) Nausea No 3868 (96.9) 3418 (98.0) 7286 (97.4) 0.004 0.64 (0.47 - 0.86) Yes 124 (3.1) 70 (2.0) 194 (2.6) Vomiting No 3963 (99.3) 3463 (99.3) 7426 (99.3) 1.000 0.99 (0.58 - 1.69) Yes 29 (0.7) 25 (0.7) 54 (0.7) Dyspepsia No 2932 (73.4) 2688 (77.1) 5620 (75.1) <0.001 0.82 (0.74 - 0.91) Yes 1060 (26.6) 800 (22.9) 1860 (24.9) Satiety No 3829 (95.9) 3365 (96.5) 7194 (96.2) 0.233 0.86 (0.68 - 1.09) Yes 163 (4.1) 123 (3.5) 286 (3.8) Indigestion No 3878 (97.1) 3420 (98.1) 7298 (97.6) 0.014 0.68 (0.50 - 0.92) Yes 114 (2.9) 68 (1.9) 182 (2.4) LOA No 3941 (98.7) 3463 (99.3) 7404 (99.0) 0.022 0.56 (0.34 - 0.92) Yes 51 (1.3) 25 (0.7) 76 (1.0) LOW No 3889 (97.4) 3425 (98.2) 7314 (97.8) 0.029 0.69 (0.51 - 0.95) Yes 103 (2.6) 63 (1.8) 166 (2.2) Coffeeground No 3986 (99.8) 3485 (99.9) 7471 (99.9) 0.641 0.57 (0.14 – 2.29) Yes 6 (0.2) 3 (0.1) 9 (0.1) Melena No 3967 (99.4) 3470 (99.5) 7437 (99.4) 0.634 0.82 (0.45 – 1.51) Yes 25 (0.6) 18 (0.5) 43 (0.6) Symptomatic No 2404 (60.2) 2295 (65.8) 4699 (62.8) <0.001 0.79 (0.72 -0.86) Yes 1588 (39.8) 1193 (34.2) 2781 (37.2) ConclusionsWe hypothesize that patients with intestinal metaplasia and atrophic gastritis may have less acid secretion, and correspondingly fewer reflux symptoms. Although many patients in clinical practice, are scoped for dyspepsia and reflux symptoms, our data suggest that patients with GIM are less likely to have these symptoms and yet harbour this pre-malignant condition of the stomach.

Rapid demographic shifts and socio-economic changes are fuelling concerns over the inadequate supply of informal care – the most common source of care-giving for older people in China. Unmet long-term care needs, which are believed to cause numerous adverse effects on health, continue to increase. Drawing data from the 2015 wave of the China Health and Retirement Longitudinal Survey, this study explores the relationship between informal care provision and unmet long-term care needs among older people in China. We first examine the availability of informal care among older people with disabilities. We then analyse whether a higher intensity of informal care leads to lower unmet needs. Our findings suggest that the majority of older people with disabilities receive a low intensity of care, i.e. less than 80 hours per month. Besides, a higher intensity of informal care received could significantly lower the probabilities of unmet needs for the disabled older adults who have mainly instrumental activities of daily living limitations. Our study points out that informal care cannot address the needs of those who are struggling with multi-dimensional difficulties in their daily living. Our findings highlight a pressing need for the government to buttress the formal care provision and delivery systems to support both informal care-givers and disabled older people in China.

Due to the energy shortage and global warming, modern manufacturing enterprises have had to face the competition from complex and ever-changing markets and the challenge of energy saving and pollution reduction. This paper studies a typical two-agent scheduling problem with energy-aware consideration, which includes a type of online agent that requires completion of its jobs as early as possible and the other type of offline agent that requires periodic completion of its jobs. We have proposed a Multi-Objective Hybrid Genetic Algorithm (MOHGA) to solve this two-agent scheduling problem where the agents’ completion times and the manufacturer’s energy consumption are the optimized objectives. The proposed MOHGA introduces the Particle Swarm Optimization (PSO) process to avoid immature convergence trap. Results from numerical experiments show this algorithm is superior to the Non-dominated Sorting Genetic Algorithm II and multi-objective PSO. With the help of MOHGA, the energy-saving schemes ‘turn-off’ and ‘velocity control’ can achieve at least 2.2% and 4.7% energy consumption reduction respectively in two-agent scheduling problem. Further numerical analysis shows that for some special cases a much greater energy-saving potential (approximately 49.1%) can be explored if proper postpone (8.4%) of the completion of the jobs is acceptable.

Background Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. Results Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement ( P  = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) ( P  = 0.016). An in-house library construction ensured accurate species identification for all isolates. Conclusions The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis , with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia . Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis . For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes.

Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C‐Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM‐affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14–16, embryos from both normal and ARM groups underwent spatial transcriptome sequencing, which identified key genes and signalling pathways. Rack1 exhibited significant interactions among differentially expressed genes on GDs 15 and 16. Reduced Rack1 expression in the ARM‐affected hindgut, verified by Rack1 silencing in intestinal epithelial cells, led to increased P38 phosphorylation and activation of the MAPK signalling pathway. The suppression of this pathway downregulated Nqo1 and Gpx4 expression, resulting in elevated intracellular levels of ferrous ions, reactive oxygen species (ROS) and lipid peroxides. Downregulation of Gpx4 expression in the ARM hindgut, coupled with Rack1 co‐localisation and consistent mitochondrial morphology, indicated ferroptosis. In summary, Rack1, acting as a hub gene, modulates ferrous ions, lipid peroxides, and ROS via the P38‐MAPK/Nqo1/Gpx4 axis. This modulation induces ferroptosis in intestinal epithelial cells, potentially influencing hindgut development during ARM onset. Spatial transcriptome sequencing of normal and anorectal malformation (ARM) rat embryos revealed that Rack1, as a hub gene, was decreased in the ARM hindgut on GD15 and GD16, and increased intracellular ferrous ions, reactive oxygen species, and lipid peroxides through the P38/Nqo1/Gpx4 axis, inducing ferroptosis in intestinal epithelial cells, which may affect the hindgut development in rat with ARM.

Chemo-resistance is the leading cause of failure in cancer therapy, however, much remains to be understood about the intrinsic mechanisms. In the present study, we discovered the novel miR-4443 that regulated malignancy of breast cancer both in vitro and in vivo. We examined the expression of miR-4443 in MDA-MB-231/S and MDA-MB-231 Epirubicin-resistant cell lines with 76 breast cancer formalin-fixed paraffin-embedded tissues by real-time PCR. Also, we investigated the loss- and gain-functions of miR-4443 by MTT assay and flow cytometry. Furthermore, we detected miR-4443 mediated tissue inhibitor of metalloproteinase 2 expression in cells by TargetScan, RT-qPCR and western blot. We identified the up-regulated expression of miR-4443 in Epi-resistant cell lines versus MDA-MB-231/S cell(Epi versus S) and in post-chemotherapy FFPE tissues, along with statistically differential expressions in PR(partial response) versus SD(stable disease)/PD(progressive disease) patients. Overexpression of miR-4443 increased the IC50 value of Epi for the target cells transfected, while inhibition of miR-4443 could restored sensitivity of the target cells to Epi. Besides, down-regulation of endogenous miR-4443 by miRNA-inhibitors significantly enhanced Epi-induced apoptosis while up-regulation of miR-4443 by miRNA-mimics lead to less Epi-induced apoptotic cells. Consequently, changes in TIMP2 mRNA and protein expression revealed that miR-4443 mimics suppressed expression of TIMP2 and induced migration in breast cancer cells. Furthermore, TIMP2 expression associated with better prognosis(HR = 0.721, 95%CI: 0.529-0.983). We revealed that miR-4443 induced malignancy of breast cancer mainly in chemo-resistance aspect for the very first time, providing a novel biomarker in breast cancer diagnosis and therapy.