[Impact of Climate Warming on Paddy Soil Organic Carbon Change in the Sichuan Basin of China].

Climate warming can increase soil temperature and lead to soil carbon release, but it can also increase soil organic carbon by increasing primary productivity. Cropland soils are considered to have a huge potential to sequester carbon; however, direct observations for the responses of cropland soil organic carbon to climate warming over broad geographic scales are rarely documented. Paddy soil is one of the important cultivated soils in China. Based on the data of 2217 sampling points obtained during the second national soil survey and the data of 2382 sampling points collected during 2017-2019, this study analyzed the change characteristics of soil organic carbon content of paddy surface soil in Sichuan Basin of China and explored the relationships between the soil organic carbon change of paddy soil and temperature, precipitation, cropland use type, fertilization intensity, and grain yield. The results showed that the content of soil organic carbon of paddy soil changed from 13.33 g·kg-1to 15.96 g·kg-1, with an increase of 2.63 g·kg-1, suggesting that soils in the Sichuan Basin have acted as a carbon sink over past 40 years. The soil organic carbon increment of paddy soil varied with different geomorphic regions and different secondary basins. The increase in SOC content in paddy soil was positively correlated with annual average temperature; negatively correlated with annual average precipitation; and initially increased and then decreased with annual average fertilizer application, annual average increase rate of fertilizer application, annual average grain yield, and annual average grain yield growth rate. The relationship between the increase in SOC content and the annual average temperature growth rate was different under different farmland utilizations, and the increase in the annual average temperature growth rate had significant effects with the increase in SOC content only on paddy-dryland rotation. These results indicate that the paddy soil organic carbon change in Sichuan Basin was co-affected by various factors, but climate warming was an important factor leading to the paddy soil organic carbon change, and its influence was controlled by the water conditions determined by farmland use.

Synthesis and Biological Activities of Oxazolidinone Pleuromutilin Derivatives as a Potent Anti-MRSA Agent.

A series of pleuromutilin derivatives containing an oxazolidinone skeleton were synthesized and evaluated in vitro and in vivo as antibacterial agents. Most of the synthesized derivatives exhibited potent antibacterial activities against three strains of Staphylococcus aureus (including MRSA ATCC 33591, MRSA ATCC 43300, and MSSA ATCC 29213) and two strains of Staphylococcus epidermidis (including MRSE ATCC 51625 and MSSE ATCC 12228). Compound 28 was the most active antibacterial agent in vitro (MIC = 0.008-0.125 µg·mL-1) and exhibited a significant bactericidal effect, low cytotoxicity, and weak inhibition (IC50 = 20.66 µmol·L-1) for CYP3A4, as well as exhibited less possibility to cause bacterial resistance. Furthermore, in vivo activities indicated that the compound was effective in reducing MRSA load in a murine thigh infection model. Moreover, it clearly facilitated the healing of MRSA skin infection and inhibited the secretion of the TNF-α, IL-6, and MCP-1 inflammatory factors in serum. These results suggest that oxazolidinone pleuromutilin is a promising therapeutic candidate for drug-resistant bacterial infections.

Tormentic acid, a triterpenoid isolated from the fruits of Chaenomeles speciose, protected indomethacin-induced gastric mucosal lesion via modulating miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho a/MLC pathway.

CONTEXT: Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. OBJECTIVE: To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. MATERIALS AND METHODS: TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. RESULTS: TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. DISCUSSION AND CONCLUSIONS: TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.

A Case of Invasive Fungal Infection Due to Scedosporium apiospermum in a Patient with Psoriasis.

Scedosporium apiospermum (S. apiospermum) is typically reported to be involved in superficial and subcutaneous fungal infections but overlooked in invasive infections, which is associated with a high mortality rate. It poses a diagnostic challenge due to its confusable characteristics to other hyaline hyphomycetes. Here, we reported a psoriasis patient with an invasive S. apiospermum infection. The patient presents an abscess at the intermuscular space of the left hip and an increased C-reactive protein level. Pus culture showed white-greyish, cottonlike colonies with aerial mycelium and terminal oval conidia, suggesting S. apiospermum. This rare fungus was rapidly confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and RNA sequencing. The patient was successfully treated with voriconazole with no recurrence of the abscesses despite delayed treatment. This is the first such case infection report from China that described an unusual case of intermuscular space abscesses due to S. apiospermum. This report highlights the possibility of fungal infections in deeper tissue, as well as the necessity of thorough evaluation and microbiological diagnosis for invasive infections, particularly in immunocompromised patients.

Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis.

BACKGROUND: Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC). AIM: To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications. METHODS: According to the inclusion and exclusion criteria, 27 patients with ALC and 24 healthy controls (HCs) were selected, and plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces. Also, the correlation between metabolites and clinical features was analyzed. RESULTS: More than 300 common metabolites were identified in the plasma and feces of patients with ALC. Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways. Compared to HCs, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. Moreover, we established a P/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score. CONCLUSION: The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC. These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia.

Aplastic anemia (AA) is a life-threatening disease characterized by bone marrow (BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells (ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA. N-acetyl-L-cysteine (NAC, a reactive oxygen species scavenger) or exogenous EC infusion was administered to AA mice. Furthermore, the frequency and functions of BM ECs from AA patients and healthy donors were evaluated. BM ECs from AA patients were treated with NAC in vitro, and then the functions of BM ECs were evaluated. We found that BM ECs were significantly decreased and damaged in AA mice. Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized, whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice. Consistently, BM ECs in AA patients were decreased and dysfunctional. Furthermore, dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes, which could be repaired by NAC in vitro. The reactive oxygen species pathway was activated, and hematopoiesis- and immune-related signaling pathways were enriched in BM ECs of AA patients. In conclusion, our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA, suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.

NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis.

BACKGROUND: Macrophages are involved in various immune inflammatory disease conditions. This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis (NEC). METHODS: CD68, nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease-1 (caspase-1), and interleukin-1ß (IL-1ß) in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry, immunofluorescence, and western blot. Hypertonic pet milk, hypoxia and cold stimulation were used to establish a mouse (wild type and Nlrp3-/-) model of NEC. The mouse macrophage (RAW 264.7) and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments. Macrophages, intestinal epithelial cell injuries, and IL-1ß release were determined. RESULTS: Compared to the gut "healthy" patients, the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3, caspase-1, and IL-1ß levels. Furthermore, in vivo, the survival rate of Nlrp3-/- NEC mice was dramatically improved, the proportion of intestinal macrophages was reduced, and intestinal injury was decreased compared to those of wild-type NEC mice. NLRP3, caspase-1, and IL-1ß derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries. CONCLUSIONS: Macrophage activation may be essential for NEC development. NLRP3/caspase-1/IL-1ß cellular signals derived from macrophages may be the underlying mechanism of NEC development, and all these may be therapeutic targets for developing treatments for NEC.

A Systematic Review of Exercise Therapy for Bowel Preparation: Evidence to Guide Practice.

This systematic review aims to evaluate (1) the effectiveness of exercise therapy in bowel preparation for colonoscopy, and (2) the characteristics of exercise programs for bowel preparation. Systematic searches were done in PubMed, EMBASE, the Cochrane Library, Web of Science, and CINAHL from inception to November 2022. Randomized controlled trials and quasi-experimental studies assessing the efficacy of exercise during bowel preparation were included in this review. Two reviewers independently assessed the methodological quality using a modified Downs and Black checklist. A narrative synthesis was conducted. A total of five studies (1,109 participants) were included in this review. In all eligible studies, the characteristics of the exercise programs varied and included mainly two types of exercise (walking and yoga), various amount of exercise (3,000-10,000 steps or 0.5-1.9 hours), and two exercise timing (during and 1 hour after taking the laxative). Available evidence indicated that exercise therapy is effective in improving the quality of bowel preparation. However, there was insufficient high-quality evidence to conclude the effects on procedure-related indicators, adverse events, and willingness to repeat preparation. Exercise should be recommended as an important part of routine bowel preparation for patients undergoing colonoscopy to improve the quality of bowel preparation. More rigorous studies focusing on the effects on procedure-related indicators, adverse events, and willingness to repeat preparation are needed. To ensure the effectiveness and safety of the intervention, it is critical to establish a standard, well-structured exercise program for bowel preparation.

Expanded clinical-grade NK cells exhibit stronger effects than primary NK cells against HCMV infection.

Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules; stronger cytotoxicity against HCMV-infected fibroblasts; and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32-0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18-0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.

Successful LC-MS/MS assay development and validation for determination of valproic acid and its metabolites supporting proactive pharmacovigilance.

Valproic acid (VPA) is a well-documented contributor to liver injury, which is likely caused by the formation of its toxic metabolites. Monitoring VPA and its metabolites is very meaningful for the pharmacovigilance, but the availability of a powerful assay is a prerequisite. In this study, for the first time, a sensitive and specific LC-MS/MS method was developed and validated to simultaneously quantify the concentrations of VPA and its six pestering isomer metabolites (3-OH-VPA, 4-OH-VPA, 5-OH-VPA, 2-PGA, VPA-G, and 2-ene-VPA) in human plasma, using 5-OH-VPA-d7 and VPA-d6 as the internal standards (ISs). We also figured out another tricky problem that the concentrations of the parent drug and the metabolites vary widely. Of note, after protein precipitation and dilution with acetonitrile (ACN) and 50% ACN successively, the analytes and the ISs were successfully separated on a Kinetex C18 column. Intriguingly, sacrificing its signal intensity by elevated collision energy of VPA finally achieved the simultaneous determination. As expected, the method showed great linearity (r > 0.998) over the concentration ranges for all analytes. The inter-day and intra-day accuracy and precision were both acceptable. The method was successfully applied in 127 children with epilepsy. This novel assay will support the VPA-associated pharmacovigilance in the future.

Case Report: Double trouble: a rare case of successfully treated Mycoplasma hominis and Pseudomonas aeruginosa co-infection.

Background: Extra-urogenital infections due to Mycoplasma hominis (M. hominis) are rare, particularly co-infection with Pseudomonas aeruginosa (P. aeruginosa). Herein, we report on a patient who was co-infected and successfully treated despite delayed treatment. Case presentation: We reported the case of a 43-year-old man with M. hominis and P. aeruginosa co-infection after a traffic accident. The patient developed a fever and severe infection despite postoperative antimicrobial therapies. The blood culture of wound tissues was positive for P. aeruginosa. Meanwhile, culturing of blood and wound samples showed pinpoint-sized colonies on blood agar plates and fried-egg-type colonies on mycoplasma medium, which were identified as M. hominis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA sequencing. Based on antibiotic susceptibility and symptoms, ceftazidime-avibactam and moxifloxacin were administered for P. aeruginosa infection. Meanwhile, after the failure of a series of anti-infective agents, M. hominis and P. aeruginosa co-infection was successfully treated with a minocycline-based regimen and polymyxin B. Conclusion: The co-infection with M. hominis and P. aeruginosa was successfully treated with anti-infective agents despite delayed treatment, providing information for the management of double infection.

Effects of N and P additions on twig traits of wild apple (Malus sieversii) saplings.

BACKGROUND: Wild apple (Malus sieversii) is under second-class national protection in China and one of the lineal ancestors of cultivated apples worldwide. In recent decades, the natural habitation area of wild apple trees has been seriously declining, resulting in a lack of saplings and difficulty in population regeneration. Artificial near-natural breeding is crucial for protecting and restoring wild apple populations, and adding nitrogen (N) and phosphorous (P) is one of the important measures to improve the growth performance of saplings. In this study, field experiments using N (CK, N1, N2, and N3: 0, 10, 20, and 40 g m- 2 yr- 1, respectively), P (CK, P1, P2, and P3: 0, 2, 4, and 8 g m- 2 yr- 1, respectively), N20Px (CK, N2P1, N2P2, and N2P3: N20P2, N20P4 and N20P8 g m- 2 yr- 1, respectively), and NxP4 (CK, N1P2, N2P2, and N3P2: N10P4, N20P4, and N40P4 g m- 2 yr- 1, respectively) treatments (totaling 12 levels, including one CK) were conducted in four consecutive years. The twig traits (including four current-year stem, 10 leaf, and three ratio traits) and comprehensive growth performance of wild apple saplings were analyzed under different nutrient treatments. RESULTS: N addition had a significantly positive effect on stem length, basal diameter, leaf area, and leaf dry mass, whereas P addition had a significantly positive effect on stem length and basal diameter only. The combination of N and P (NxP4 and N20Px) treatments evidently promoted stem growth at moderate concentrations; however, the N20Px treatment showed a markedly negative effect at low concentrations and a positive effect at moderate and high concentrations. The ratio traits (leaf intensity, leaf area ratio, and leaf to stem mass ratio) decreased with the increase in nutrient concentration under each treatment. In the plant trait network, basal diameter, stem mass, and twig mass were tightly connected to other traits after nutrient treatments, indicating that stem traits play an important role in twig growth. The membership function revealed that the greatest comprehensive growth performance of saplings was achieved after N addition alone, followed by that under the NxP4 treatment (except for N40P4). CONCLUSIONS: Consequently, artificial nutrient treatments for four years significantly but differentially altered the growth status of wild apple saplings, and the use of appropriate N fertilizer promoted sapling growth. These results can provide scientific basis for the conservation and management of wild apple populations.

Predicting short-term and long-term mortalities from sepsis in patients who receive allogeneic haematopoietic stem cell transplantation.

Patients who receive allogeneic haematopoietic stem cell transplantation (allo-HSCT) may develop sepsis, which result in a highly intensive care unit admission rate and mortality. Therefore, short-term and long-term prognostic models for sepsis after allo-HSCT are urgently needed. We enrolled patients receiving allo-HSCT who developed sepsis after allo-HSCT at Peking University People's Hospital between 2012 and 2021, including 287 patients who received allo-HSCT in 2018-2021 in the derivation cohort, and 337 patients in 2012-2017 in the validation cohort. Multivariate logistic regression analysis was used to identify prognostic factors, and these identified factors were incorporated into two scoring models. Seven independent factors (acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD), total bilirubin, lactate dehydrogenase (LDH) and organ dysfunction [renal, lung and heart]) were included in the 6-month prognostic model, and six factors (cGVHD, C-reactive protein, LDH, organ dysfunction [lung, neurologic and coagulation]) were included in the 14-day prognostic model. The area under the receiver operating characteristic curves, calibration plots and decision curve analysis demonstrated the robust predictive performance of the models, better than the Sequential Organ Failure Assessment score. Early identification of patients with high risk of 6-month and 14-day death may allow clinicians to provide timely treatments and improve the therapeutic effects.

Avapritinib is effective for treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and kit mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation.

In patients with t(8;21) acute myeloid leukemia (AML) with recurrent measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), pre-emptive interferon-α therapy and donor lymphocyte infusion are noneffective in 30%-50% of patients. Avapritinib is a novel tyrosine kinase inhibitor targeting KIT mutations. We retrospectively report about 20 patients with t(8;21) AML and KIT mutations treated with avapritinib after allo-HSCT with MRD and most failing to respond to immunotherapy. Reduction of RUNX1-RUNX1T1 after 1 month of treatment was ≥1 log in 12 patients (60%), which became negative in 4 patients (20%). In 13 patients who received avapritinib for ≥3 months, the reduction was ≥1 log in all patients, which became negative in 7 patients (53.8%). The median follow-up time was 5.5 (2.0-10.0) months from avapritinib initiation to the last follow-up. Three patients underwent hematologic relapse and survived. Among all 20 patients, RUNX1-RUNX1T1 transcripts turned negative in 9 patients (45%). The efficacy did not differ significantly between D816 and non-D816 KIT mutation groups. The main adverse effect was hematological toxicity, which could generally be tolerated. In summary, avapritinib was effective for MRD treatment in patients with t(8;21) AML with KIT mutations failing to respond to immunotherapy after allo-HSCT.

Harmonics of Parton Saturation in Lepton-Jet Correlations at the Electron-Ion Collider.

Parton saturation is one of the most intriguing phenomena in the high energy nuclear physics research frontier, especially in the upcoming era of the Electron-Ion Collider (EIC). The lepton-jet correlation in deep inelastic scattering provides us with a new gateway to the parton saturation at the EIC. In particular, we demonstrate that azimuthal angle anisotropies of the lepton-jet correlation are sensitive to the strength of the saturation momentum in the EIC kinematic region. In contrast to the predictions based on the collinear framework calculation, significant nuclear modification of the anisotropies is observed when we compare the saturation physics results in e+p and e+Au scatterings. By measuring these harmonic coefficients at the EIC, one can conduct quantitative analyses in different collisional systems and unveil compelling evidence for saturation effects.

BDNF signaling in correlation-dependent structural plasticity in the developing visual system.

During development, patterned neural activity instructs topographic map refinement. Axons with similar patterns of neural activity converge onto target neurons and stabilize their synapses with these postsynaptic partners, restricting exploratory branch elaboration (Hebbian structural plasticity). On the other hand, non-correlated firing in inputs leads to synapse weakening and increased exploratory growth of axons (Stentian structural plasticity). We used visual stimulation to control the correlation structure of neural activity in a few ipsilaterally projecting (ipsi) retinal ganglion cell (RGC) axons with respect to the majority contralateral eye inputs in the optic tectum of albino Xenopus laevis tadpoles. Multiphoton live imaging of ipsi axons, combined with specific targeted disruptions of brain-derived neurotrophic factor (BDNF) signaling, revealed that both presynaptic p75NTR and TrkB are required for Stentian axonal branch addition, whereas presumptive postsynaptic BDNF signaling is necessary for Hebbian axon stabilization. Additionally, we found that BDNF signaling mediates local suppression of branch elimination in response to correlated firing of inputs. Daily in vivo imaging of contralateral RGC axons demonstrated that p75NTR knockdown reduces axon branch elongation and arbor spanning field volume.

Major depressive disorder is correlated with the mitochondrial ND1 T3394C mutation in two Han Chinese families: Two case reports.

BACKGROUND: Major depressive disorder (MDD) is the most frequent reason of disabled people in the world, as reported by the World Health Organization. However, the diagnosis of MDD is mainly based on clinical symptoms. CASE SUMMARY: The clinical, genetic, and molecular characteristics of two Chinese families with MDD are described in this study. There were variable ages of onset and severity in depression among the families. Both Chinese families had a very low pre-valence of MDD. The mitochondrial genomes of these pedigrees were sequenced and indicated a homoplasmic T3394C (Y30H) mutation, with the polymorphism located at a highly conserved tyrosine at position 30 of ND1. The analysis also revealed unique sets of mitochondrial DNA (mtDNA) polymorphisms orig-inating from haplogroups M9a3 and M9a. CONCLUSION: This finding of the T3394C mutation in two unrelated depressed patients provides strong evidence that this mutation may have a part in the etiology of MDD. However, In these two Chinese families having the T3394C mutation, no functional mtDNA mutation was observed. Therefore, T3394C mutations are related with MDD, and the phenotypic manifestation of these mutations may be affected by changes in nuclear genes or environmental factors.

Investigating the induction of polyphenol biosynthesis in the cultured Cycolocarya paliurus cells and the stimulatory mechanism of co-induction with 5-aminolevulinic acid and salicylic acid.

Background: Plant cell culture technology is a potential way to produce polyphenols, however, this way is still trapped in the dilemma of low content and yield. Elicitation is regarded as one of the most effective ways to improve the output of the secondary metabolites, and therefore has attracted extensive attention. Methods: Five elicitors including 5-aminolevulinic acid (5-ALA), salicylic acid (SA), methyl jasmonate (MeJA), sodium nitroprusside (SNP) and Rhizopus Oryzae Elicitor (ROE) were used to improve the content and yield of polyphenols in the cultured Cyclocarya paliurus (C. paliurus) cells, and a co-induction technology of 5-ALA and SA was developed as a result. Meanwhile, the integrated analysis of transcriptome and metabolome was adopted to interpret the stimulation mechanism of co-induction with 5-ALA and SA. Results: Under the co-induction of 50 µM 5-ALA and SA, the content and yield of total polyphenols of the cultured cells reached 8.0 mg/g and 147.12 mg/L, respectively. The yields of cyanidin-3-O-galactoside, procyanidin B1 and catechin reached 28.83, 4.33 and 2.88 times that of the control group, respectively. It was found that expressions of TFs such as CpERF105, CpMYB10 and CpWRKY28 increased significantly, while CpMYB44 and CpTGA2 decreased. These great changes might further make the expression of CpF3'H (flavonoid 3'-monooxygenase), CpFLS (flavonol synthase), CpLAR (leucoanthocyanidin reductase), CpANS (anthocyanidin synthase) and Cp4CL (4-coumarate coenzyme A ligase) increase while CpANR (anthocyanidin reductase) and CpF3'5'H (flavonoid 3', 5'-hydroxylase) reduce, ultimately enhancing the polyphenols accumulation Conclusion: The co-induction of 5-ALA and SA can significantly promote polyphenol biosynthesis in the cultured C. paliurus cells by regulating the expression of key transcription factors and structural genes associated with polyphenol synthesis, and thus has a promising application.