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Abstract Red flesh apple (Malus pumila var. medzwetzkyana Dieck), purple leaf plum (Prunus cerasifera Ehrhar f), and purple leaf peach (Prunus persica ‘Atropurpurea’) are significant ornamental plants within the Rosaceae family. The coloration of their fruits and leaves is crucial in their appearance and nutritional quality. However, qualitative and quantitative studies on flavonoids in the succulent fruits and leaves of multicolored Rosaceae plants are lacking. To unveil the diversity and variety-specificity of flavonoids in these three varieties, we conducted a comparative analysis of flavonoid metabolic components using ultra-high-performance liquid phase mass spectrometry (UPLC-MS/MS). The results revealed the detection of 311 metabolites, including 47 flavonoids, 105 flavonols, 16 chalcones, 37 dihydroflavonoids, 8 dihydroflavonols, 30 anthocyanins, 14 flavonoid carbon glycosides, 23 flavanols, 8 isoflavones, 11 tannins, and 12 proanthocyanidins. Notably, although the purple plum and peach leaves exhibited distinct anthocyanin compounds, paeoniflorin and corythrin glycosides were common but displayed varying glycosylation levels. While the green purple leaf peach fruit (PEF) and red flesh apple leaf (AL) possessed the lowest anthocyanin content, they exhibited the highest total flavonoid content. Conversely, the red flesh apple fruit (AF) displayed the highest anthocyanin content and a diverse range of anthocyanin glycosylation modifications, indicating that anthocyanins predominantly influenced the fruit's color. Purple PLF, PLL, and PEL showcased varying concentrations of anthocyanins, suggesting that their colors result from the co-color interaction between specific types of anthocyanins and secondary metabolites, such as flavonols, flavonoids, and dihydroflavonoids. This study provides novel insights into the variations in tissue metabolites among Rosaceae plants with distinct fruit and leaf colors.

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People’s Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People’s Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13–0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17–0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21–1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

Abstract Anti-oxidant stress is a potential strategy for the treatment of ischemic stroke. Here, we found a novel free radical scavenger termed as CZK, which is derived from alkaloids contained in Clausena lansium. In this study, we first compared cytotoxicity and biological activity between CZK and its parent’s compound Claulansine F. It was found that CZK had lower cytotoxicity and improved anti-oxygen–glucose deprivation/reoxygenation (OGD/R) injury than its parent’s compound. Free radical scavenging test showed that CZK had a strong inhibitory effect on hydroxyl free radicals with the IC50 of 77.08 nM. Intravenous injection of CZK (50 mg/kg) significantly alleviated ischemia–reperfusion injury, manifested by reduced neuronal damage and decreased oxidative stress. Consistent with the findings, the activities of superoxide dismutase (SOD) and reduced glutathione (GSH) were increased. Molecular docking predicted that CZK might be combined with nuclear factor erythroid 2-related factor 2 (Nrf2) complex. Our results also confirmed that CZK upregulated the contents of Nrf2 and its target gene products Heme Oxygenase-1 (HO-1), and NAD(P)H: Quinone Oxidoreductase 1 (NQO1). In conclusion, CZK had a potential therapeutic effect for ischemic stroke by activating Nrf2-mediated antioxidant system.

Abstract Background Cultivation of resistant rootstocks can effectively prevent apple replant disease (ARD), and grafting tests are an important means of evaluating the compatibility of rootstocks with scions. Methods The apple rootstocks 12–2 (self-named) and Malus hupehensis Rehd. (PYTC) were planted in a replanted 20-year-old apple orchard. The two rootstocks were grafted with scions of 13 apple varieties. Multiple aboveground physiological parameters of the grafted combinations were measured and evaluated to verify the grafting affinity of 12–2 with the scions as compared to Malus hupehensis Rehd. (PYTC). Results The graft survival rate and graft interface healing of 12–2 did not differ significantly from those of PYTC. Mechanical strength tests of the grafted interfaces showed that some mechanical strength indices of Redchief, Jonagold, Starking, Goldspur and Yinv apple varieties were significantly higher when they were grafted onto 12–2 compared to the PYTC control. The height and diameter of shoots and the relative chlorophyll content, photosynthetic and fluorescence parameters, antioxidant enzyme activities and malondialdehyde content of leaves showed that Fuji 2001, Tengmu No.1, RedChief, Gala, USA8, and Shoufu1 grew similarly on the two rootstocks, but Tianhong 2, Lvguang, Jonagold, Starking, Goldspur, Yinv and Luli grew better when grafted onto 12–2 than onto the PYTC control. The rootstock 12-2, therefore, showed good grafting affinity. Conclusion These results provide experimental materials and theoretical guidance for the cultivation of a new grafting compatible rootstock to the 13 studied apple cultivars.

Abstract Background Elaeagnus angustifolia L. is a deciduous tree in the family Elaeagnaceae. It is widely used to study abiotic stress tolerance in plants and to improve desertification-affected land because of its ability to withstand diverse types of environmental stress, such as drought, salt, cold, and wind. However, no studies have examined the mechanisms underlying the resistance of E. angustifolia to environmental stress and its adaptive evolution. Methods Here, we used PacBio, Hi-C, resequencing, and RNA-seq to construct the genome and transcriptome of E. angustifolia and explore its adaptive evolution. Results The reconstructed genome of E. angustifolia was 526.80 Mb, with a contig N50 of 12.60 Mb and estimated divergence time of 84.24 Mya. Gene family expansion and resequencing analyses showed that the evolution of E. angustifolia was closely related to environmental conditions. After exposure to salt stress, GO pathway analysis showed that new genes identified from the transcriptome were related to ATP-binding, metal ion binding, and nucleic acid binding. Conclusion The genome sequence of E. angustifolia could be used for comparative genomic analyses of Elaeagnaceae family members and could help elucidate the mechanisms underlying the response of E. angustifolia to drought, salt, cold, and wind stress. Generally, these results provide new insights that could be used to improve desertification-affected land.

Browning is a major problem in the tissue culture of woody plants. Previous studies have shown that nitric oxide (NO) plays a role in regulating plant responses to stress, but its effect on browning in the tissue culture of Malus remains unclear. This study aimed to investigate the impact of exogenous NO donor sodium nitroprusside (SNP) on the browning of Malus sieversii stem tip explants. The results demonstrated that the addition of 50 μM SNP significantly reduced explant browning. Further analysis revealed that exogenous NO decreased the browning index (BD) and levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion radical O2−. Additionally, NO treatment increased the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX). NO treatment also enhanced the activity of phenylalanine ammonia lyase (PAL), which contributed to the accumulation of flavonoids and inhibited the activity of polyphenol oxidase (PPO) and peroxidase (POD), which are key enzymes involved in the browning process. Furthermore, 50 μM SNP significantly promoted the accumulation of non-enzymatic antioxidants such as proline (Pro), soluble sugar (SS), and soluble protein (SP). Therefore, the results suggest that NO is able to counteract excessive reactive oxygen species (ROS) damage by enhancing both the enzymatic and non-enzymatic antioxidant systems, resulting in a reduction in browning in stem tip explants. Consequently, an improvement in the in vitro propagation efficiency of Malus sieversii shoot tip explants can be achieved.

ObjectiveThe aim of this study was to examine whether osteoporosis (OP) is associated with Alzheimer’s disease-related cerebrospinal fluid (CSF) biomarkers and brain structures among older people.MethodsFrom the Alzheimer’s disease Neuroimaging Initiative database, we grouped participants according to the OP status (OP+/OP−) and compared the Alzheimer’s disease (AD)-related CSF biomarker levels and the regional brain structural volumes between the two groups using multivariable models. These models were adjusted for covariates including age, education, gender, diagnosis of Alzheimer’s disease, and apolipoprotein E4 carrier status.ResultsIn the cross-sectional analyses at baseline, OP was related to higher CSF t-tau (total tau) and p-tau181 (tau phosphorylated at threonine-181) but not to CSF amyloid-beta (1–42) or the volumes of entorhinal cortex and hippocampus. In the longitudinal analyses, OP was not associated with the change in the three CSF biomarkers over time but was linked to a faster decline in the size of the entorhinal cortex and hippocampus.ConclusionOP was associated with elevated levels of CSF t-tau and p-tau181 at baseline, and accelerated entorhinal cortex and hippocampal atrophies over time among older people.

Abstract Ultra‐dense networking is considered an effective solution to achieve high capacity in 5G networks. However, the densely distributed base stations (BSs) in ultra‐dense networks (UDNs) make the inter‐cell interference much more serious than that in traditional cellular networks. Therefore, it is important to mitigate inter‐cell interference in the UDNs to improve network performance. To tackle this problem, we propose a novel virtual resource mapping algorithm that includes a resource reservation (RR) algorithm and a real‐time resource embedding (RE) algorithm. Specifically, according to the number of services predicted by a dynamic service model, the RR algorithm is proposed to determine the sets of multiplexing BSs in the next time cycle and reserve channel resource required by each BS. Then, to further reduce inter‐cell interference, the real‐time RE algorithm is proposed to allocate the channel resource in real time. Finally, simulation results show that the proposed algorithm has better performance in terms of signal‐to‐interference‐plus‐noise ratio and acceptance ratio, compared to the existing algorithms, such as the frequency reuse channel allocation algorithm and inter‐cell interference coordination algorithm.

Potassium channels are important ion channels that are responsible for the absorption of potassium in the plant nutrient uptake system. In this study, we used homologous molecular cloning to obtain 8 K+ channel genes from the superior apple rootstock line 12-2 (self-named): MsAKT1-1, MsKAT3-2, MsKAT1-3, MsK2P3-4, MsK2P3-5, MsK2P5-6, MsK2P3-7, and MsK2P3-8. Their lengths varied from 942 bp (MsK2P5-6) to 2625 bp (MsAKT1-1), and the number of encoded amino acids varied from 314 (MsK2P5-6) to 874 (MsAKT1-1). Subcellular localization predictions showed that MsAKT1-1, MsKAT3-2, and MsKAT1-3 were localized on the plasma membrane, and MsK2P3-4, MsK2P3-5, MsK2P5-6, MsK2P3-7, and MsK2P3-8 were localized on the vacuole and plasma membrane. The 8 K+ channel proteins contained α helices, extended strands, β turns, and random coils. MsKAT1-3 had four transmembrane structures, MsKAT3-2 had six, and the other six K+ channel genes had five. Protein structure domain analysis showed that MsAKT1-1 contained nine protein domains, followed by MsKAT3-2 with four, MsKAT1-3 with three, and the other five two-pore domain K+ channel proteins with two. Semi-quantitative RT-PCR detection of the K+ channel genes showed that their expression levels were high in roots. qRT-PCR analysis showed that the relative expression levels of the 8 genes changed after exposure to ARD stress. The above results provide a theoretical basis for further research on the functions of potassium channel genes in 12-2 and a scientific basis for the breeding of ARD-resistant rootstock.

The cultivation of resistant rootstocks is one of the more effective ways to mitigate apple replant disease (ARD). We performed an ion current test, a pot experiment, and a pathogen infection test on the apple rootstocks 12-2 (self-named), T337, and M26. The ion current test showed that exposure to ARD soil extract for 30 min had a significant effect on K+ ion currents at the meristem, elongation, and mature zones of the M26 rhizoplane and on Ca2+ currents in the meristem and elongation zones. ARD also had a significant effect on Ca2+ currents in the meristem, elongation, and mature zones of the T337 rhizoplane. Exposure to ARD soil extract for 5 min had a significant effect on K+ currents in the meristem, elongation, and mature zones of 12-2 and on the Ca2+ currents in the elongation and mature zones. Compared to a 5-min exposure, a 30-min exposure to ARD extract had a less pronounced effect on K+ and Ca2+ currents in the 12-2 rhizoplane. The pot experiment showed that ARD soil had no significant effect on any root architectural or physiological parameters of 12-2. By contrast, ARD soil significantly reduced some root growth indices and the dry and fresh weights of T337 and M26 compared with controls on sterilized soil. ARD also had a significant effect on root metabolic activity, root antioxidant enzyme activity (except superoxide dismutase for T337), and malondialdehyde content of T337 and M26. Pathogen infection tests showed that Fusarium proliferatum MR5 significantly affected the root structure and reduced the root metabolic activity of T337 and M26. It also reduced their root antioxidant enzyme activities (except catalase for T337) and significantly increased the root malondialdehyde content, reactive oxygen levels, and proline and soluble sugar contents. By contrast, MR5 had no such effects on 12-2. Based on these results, 12-2 has the potential to serve as an important ARD-resistant rootstock.

Abstract The intake of some micronutrients is still a public health challenge for pregnant women in Finland. This study examined the effects of dietary counselling on micronutrient intakes among pregnant women at increased risk of gestational diabetes mellitus in Finland. This study utilised data from was a cluster‐randomised controlled trial (n = 399), which aimed to prevent gestational diabetes. In the intervention group, the dietary counselling was carried out at four routine visits to maternity care and focused on dietary fat, fibre and saccharose intake. A validated 181‐item food frequency questionnaire was used for evaluating the participants' food consumption and nutrient intakes. The differences in changes in micronutrient intakes from baseline (pre‐pregnancy) to 36–37 weeks' gestation were compared between the intervention and the usual care groups using multilevel mixed‐effects linear regression models, adjusted for confounders. Based on the multiple‐adjusted model, the counselling increased the intake of niacin equivalent (coefficient 0.50, 95% confidence interval [CI] 0.03–0.97), vitamin D (0.24, CI 0.05–0.43), vitamin E (0.46, CI 0.26–0.66) and magnesium (5.05, CI 0.39–9.70) and maintained the intake of folate (6.50, CI 1.44–11.56), from early pregnancy to 36 to 37 weeks' gestation. Except for folate and vitamin D, the mean intake of the micronutrients from food was adequate in both groups at baseline and the follow‐up. In conclusion, the dietary counselling improved the intake of several vitamins and minerals from food during pregnancy. Supplementation on folate and vitamin D is still needed during pregnancy.

Organic acids secreted by plants, such as p-hydroxybenzoic acid, ferulic acid, cinnamic acid, and benzoic acid, can inhibit seed germination and root growth. The effects of root and soil leaching liquor from orchards on the growth of M. hupehensis Rehd. seedlings under sand culture are studied; the seedlings are sampled at 15, 30, 45, and 60 d. Changes in the amount of root exudates are determined using HPLC. Low concentrations of root leaching liquor (A1) and soil leaching liquor (B1) significantly promoted plant growth and chlorophyll synthesis; high concentrations of root leaching liquor (A6) and soil leaching liquor (B4–6) inhibited growth. Low concentrations of soil leaching liquor had no significant effect on the POD, SOD, and CAT activities. A5–6 and B5–6 significantly decreased Fv/Fm and qP values, respectively, and increased NPQ values. All root and soil leaching liquor treatments inhibited the secretion of gallic acid, hydroxybenzoic acid, benzoic acid, and phloridzin, and promoted the secretion of caffeic acid. The root leaching liquor treatments inhibited the secretion of catechin and promoted the secretion of phloretin. The soil leaching liquor treatments promoted the secretion of cinnamic acid. The secretion of other phenolic acids is likely associated with the different concentrations of leaching liquor.

Depression is an inflammation-associated disease that results in major depression as inflammation increases and progresses. Ginsenoside Rg1 (Rg1), the major bioactive ingredient derived from ginseng, possesses remarkable anti-depressant and anti-inflammatory effects. Our previous studies showed that the pathogenesis of depression was concomitant with the acceleration of connexin43 (Cx43) ubiquitin degradation, while Rg1 could upregulate Cx43 expression to attenuate depression. However, whether the ubiquitination of Cx43 is the specific correlation between depression and inflammation, and how Rg1 ameliorates neuroinflammation to attenuate depression, are still under investigation. In in vivo experiments, Rg1 treatment significantly ameliorated depression-like behaviors in rats subjected to chronic unpredictable stress (CUS). Moreover, these CUS rats treated with Rg1 exhibited attenuated neuroinflammation, together with the suppression of Cx43 ubiquitination. In in vitro experiments, Rg1 reduced the secretion of inflammatory cytokines and the ubiquitination of Cx43 in lipopolysaccharide-induced glial cells. Furthermore, treatment with ubiquitin-proteasome inhibitor MG132 suppressing the ubiquitination of Cx43 ameliorated lipopolysaccharide-induced neuroinflammation. The results suggest that Rg1 attenuates depression-like behavioral performances in CUS-exposed rats; and the main mechanism of the antidepressant-like effects of Rg1 appears to involve protection against neuroinflammation via suppression of Cx43 ubiquitination. In conclusion, Rg1 could ameliorate neuroinflammation via suppression of Cx43 ubiquitination to attenuate depression, which represents the perspective of an innovative therapy of Rg1 in the treatment of inflammation-associated depression.

(1) Background: Cultivating resistant rootstocks is an effective way to mitigate apple replant disease (ARD), and we developed superior apple rootstock line 12-2 (self-named), which shows improved ARD resistance. (2) Methods: We used ARD-associated pathogen Fusarium proliferatum MR5 (MR5) to test the fungal infection in the 12-2 line. Seedlings of the 12-2, T337, and M26 rootstock lines were planted in a substrate with potato dextrose broth and MR5 spore solution, and aboveground physiological indicators were measured. (3) Results: MR5 had the greatest effect on the leaf growth of T337 and M26. The incidence rates of infectious symptoms in the T337 and M26 lines were 68 and 100%, respectively. MR5 significantly affected the leaf chlorophyll content, ETR, and NPQ of T337 and M26, as well as Pn and Tr of M26. MR5 tended to reduce the leaf photosynthetic parameters of T337, but the decreases were not significant. The leaf reactive-oxygen-species levels of T337 and M26, the leaf antioxidant-enzyme activities of M26, and the superoxide-dismutase activity of T337 were significantly affected by MR5. MR5 also had a significant effect on the leaf malondialdehyde, proline, and soluble-sugar contents of T337 and M26. None of these aboveground physiological indicators were affected by MR5 in the 12-2 rootstock. (4) Conclusions: The 12-2 rootstock was more resistant to ARD-associated MR5 and could serve as an important test material for resistant-apple-rootstock breeding in China.

ObjectiveTo examine whether osteoarthritis (OA) is associated with a change in adjusted hippocampal volumes (HpVR: hippocampal/intracranial volume × 103) over time among cognitively normal older people.MethodsWe examined the cross-sectional and longitudinal associations of OA with HpVR among individuals with normal cognition (NC) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. At baseline, a total of 372 individuals with NC were included.ResultsIn the cross-sectional analyses of baseline data, we did not find a significant relationship between OA and HpVR among individuals with NC. However, in the longitudinal analyses, OA was significantly associated with change in HpVR over time among individuals with NC. Specifically, compared with individuals without OA, those with OA showed a faster decline in HpVR over time when controlling for other potential confounders, including age, educational attainment, gender, and APOE4 genotype.ConclusionOA status was significantly associated with a change in HpVR over time among individuals with NC.

Traumatic hip dislocation usually occurs in young patients, with the increasing number of high-energy injuries, and 62–93% of reported adult traumatic hip dislocations were caused by high-speed motor vehicle crashes. However, ipsilateral femoral neck fractures and intertrochanteric fractures with posterior dislocation of the hip are extremely rare, and this injury poses a challenge to orthopaedic surgeons. Here, we report two cases of simultaneous ipsilateral femoral neck fracture, intertrochanteric fracture and posterior dislocation of the hip joint in young patients who were treated with proximal femoral locking compression plate (PFLCP). The long-term follow-up (one patient was followed up for 3 years and the other for 7 years) showed that these patients had excellent functional outcomes with near-normal ranges of hip movement. The authors believe that using smaller plates with the lateral PFLCP is an acceptable method to treat this injury in young patients.

(1) Background: The cultivation of resistant rootstocks is an effective way to prevent ARD. (2) Methods: 12-2 (self-named), T337, and M26 were planted in replanted and sterilized soil. The aboveground physiological indices were determined. (3) Results: The plant heights and the stem thicknesses of T337 and M26 were significantly affected by ARD. Relative chlorophyll content (June–October), Pn (August–September), and Gs (August) of T337 and relative chlorophyll content (June–July, September), Pn (September–October), and Ci (September) of M26 were significantly affected by ARD. ARD had a significant effect on Fv/Fm (June), qP (June–July), and NPQ of T337 (June–October, except August) and Fv/Fm (June) and NPQ (June-October, except July) of M26. Additionally, ARD affected Rfd of M26 and T337 during August. SOD (August and October), POD (August–September), and CAT (July-August, October) activities and MDA (September–October) content of T338 as well as SOD (July–October), POD (June–October), and CAT (July-October) activities and MDA (July, September–October) content of M26 were significantly affected by ARD. ARD significantly reduced nitrogen (October), phosphorus (September–October), and zinc (July) contents of M26 and potassium (June) content of T337. The above physiological indices were not affected by ARD in 12-2. (4) Conclusions: 12-2 could be useful as an important rootstock to relieve ARD due to strong resistance.

Background Statins may reduce mortality after transcatheter aortic valve replacement (TAVR) through prevention of atherosclerotic events or pleiotropic effects. However, the competing mortality risks in TAVR patients may dilute any positive effect of statins. We sought to understand the association of statin use with post‐TAVR mortality. Methods and Results We included high– or intermediate–surgical risk patients who underwent TAVR as a part of the PARTNER (Placement of Aortic Transcatheter Valves) II and Sapien 3 trials and registries. Outcomes included 2‐year all‐cause, cardiovascular, and noncardiovascular mortality. We used propensity score matching to generate matched pairs between those discharged on a statin and those not on a statin after TAVR. Bias was explored with falsification end points (urinary infection, hip fracture). Among 3956 patients who underwent TAVR, we matched 626 patients on a statin with 626 patients not on a statin at discharge. Among matched patients, statin use was associated with lower risk of all‐cause (hazard ratio [HR] 0.65, 95% CI 0.49‐0.87, P=0.001), cardiovascular (HR 0.66, 95% CI 0.46‐0.96, P=0.030), and noncardiovascular mortality (HR 0.64, 95% CI 0.44‐0.99, P=0.045) compared with no statin use. The survival curves diverged within 3 months and continued to separate over a median follow‐up of 2.1 years. The falsification end points were similar among groups (urinary infection, P=0.66; hip fracture, P=0.64). Conclusions In an observational, propensity‐matched analysis of TAVR patients, statin use was associated with lower rates of cardiovascular and noncardiovascular mortality compared with no statin use. Given the early emergence of the apparent protective effect of statins, this result may be driven either by pleiotropic effects or by residual confounding despite propensity‐matching methodology.

Primary inoculation tuberculosis is a skin condition that develops at the site of inoculation of Mycobacterium tuberculosis in tuberculosis-free individuals. This report describes the diagnosis, treatment and >1 year follow-up of 30 patients presenting with acupuncture-induced primary inoculation tuberculosis. Our data provide a deeper insight into this rare route of infection of tuberculosis. We also review effective treatment options.

Depression is an inflammation-associated disease that results in major depression as inflammation increases and progresses. Ginsenoside Rg1 (Rg1), the major bioactive ingredient derived from ginseng, possesses remarkable anti-depressant and antiinflammatory effects. Our previous studies showed that the pathogenesis of depression was concomitant with the acceleration of connexin43 (Cx43) ubiquitin degradation, while Rg1 could upregulate Cx43 expression to attenuate depression. However, whether the ubiquitination of Cx43 is the specific correlation between depression and inflammation, and how Rg1 ameliorates neuroinflammation to attenuate depression, are still under investigation. In in vivo experiments, Rg1 treatment significantly ameliorated depression-like behaviors in rats subjected to chronic unpredictable stress (CUS). Moreover, these CUS rats treated with Rg1 exhibited attenuated neuroinflammation, together with the suppression of Cx43 ubiquitination. In in vitro experiments, Rg1 reduced the secretion of inflammatory cytokines and the ubiquitination of Cx43 in lipopolysaccharide-induced glial cells. Furthermore, treatment with ubiquitin-proteasome inhibitor MG132 suppressing the ubiquitination of Cx43 ameliorated lipopolysaccharide-induced neuroinflammation. The results suggest that Rg1 attenuates depression-like behavioral performances in CUSexposed rats; and the main mechanism of the antidepressant-like effects of Rg1 appears to involve protection against neuroinflammation via suppression of Cx43 ubiquitination. In conclusion, Rg1 could ameliorate neuroinflammation via suppression of Cx43 ubiquitination to attenuate depression, which represents the perspective of an innovative therapy of Rg1 in the treatment of inflammation-associated depression. [ABSTRACT FROM AUTHOR]

Introduction: Chemokine-like factor 1 (CKLF1) is a chemokine that is overexpressed in several diseases. Our previous findings revealed a significant increase in CKLF1 expression in the ischemic brain, suggesting its potential as a therapeutic target for ischemic stroke. Methods: In this study, we examined the expression dynamics of CKLF1 in both in vivo and in vitro models of ischemic cardiac injury. Myocardial infarction (MI) was induced in vivo by ligation of the left anterior descending artery (LAD) of the rat heart. The levels of CKLF1, Creatine Kinase MB Isoenzyme (CK-MB), and Lactate dehydrogenase (LDH) in the serum were detected using Enzyme-linked immunosorbent assay (ELISA). The expression of CKLF1 in the infarcted area was detected by immunohistochemistry, immunofluorescence, quantitative PCR (qPCR), and Western blotting (WB). H9C2 and AC16 cardiomyocytes cultured in vitro were subjected to oxygen and glucose deprivation (OGD). LDH was used to detect cell damage, and CKLF1 expression was detected by qPCR and WB. Results: CKLF1 mRNA and protein expression were significantly increased in h9c2 cells at 1.5 h and in AC16 cells at 4 h after OGD. The serum CK-MB in rats increased significantly on the first day after infarction, while the LDH concentration increased significantly on the third day after infarction. CKLF1 blood levels significantly increased on the first day following MI in rats. CKLF1 expression notably increased in the infarct area on days 1, 3, and 7 post-MI. In MI tissue, CKLF1 colocalizes with cardiomyocytes, macrophages, and neutrophils. Conclusion: CKLF1 was substantially expressed during myocardial ischemia injury both in vivo and in vitro and was colocalized with macrophages and neutrophils, indicating that CKLF1 is expected to be a biomarker and a drug target for the treatment of myocardial infarction. [ABSTRACT FROM AUTHOR]

Malus sieversii is a precious apple germplasm resource. Browning of explants is one of the most important factors limiting the survival rate of plant tissue culture. In order to explore the molecular mechanism of the browning degree of different strains of Malus sieversii, we compared the dynamic changes of Malus sieversii and Malus robusta Rehd. during the whole browning process using a multi-group method. A total of 44 048 differentially expressed genes (DEGs) were identified by transcriptome analysis on the DNBSEQ-T7 sequencing platform. KEGG enrichment analysis showed that the DEGs were significantly enriched in the flavonoid biosynthesis pathway. In addition, metabonomic analysis showed that (-)-epicatechin, astragalin, chrysin, irigenin, isoquercitrin, naringenin, neobavaisoflavone and prunin exhibited different degrees of free radical scavenging ability in the tissue culture browning process, and their accumulation in different varieties led to differences in the browning degree among varieties. Comprehensive transcriptome and metabonomics analysis of the data related to flavonoid biosynthesis showed that PAL, 4CL, F3H, CYP73A, CHS, CHI, ANS, DFR and PGT1 were the key genes for flavonoid accumulation during browning. In addition, WGCNA analysis revealed a strong correlation between the known flavonoid structure genes and the selected transcriptional genes. Protein interaction predictions demonstrated that 19 transcription factors (7 MYBs and 12 bHLHs) and 8 flavonoid structural genes had targeted relationships. The results show that the interspecific differential expression of flavonoid genes is the key influencing factor of the difference in browning degree between Malus sieversii and Malus robusta Rehd., providing a theoretical basis for further study on the regulation of flavonoid biosynthesis. [ABSTRACT FROM AUTHOR]