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1.
Nature ; 615(7953): 652-659, 2023 03.
Article in English | MEDLINE | ID: mdl-36890232

ABSTRACT

Increasing the proportion of locally produced plant protein in currently meat-rich diets could substantially reduce greenhouse gas emissions and loss of biodiversity1. However, plant protein production is hampered by the lack of a cool-season legume equivalent to soybean in agronomic value2. Faba bean (Vicia faba L.) has a high yield potential and is well suited for cultivation in temperate regions, but genomic resources are scarce. Here, we report a high-quality chromosome-scale assembly of the faba bean genome and show that it has expanded to a massive 13 Gb in size through an imbalance between the rates of amplification and elimination of retrotransposons and satellite repeats. Genes and recombination events are evenly dispersed across chromosomes and the gene space is remarkably compact considering the genome size, although with substantial copy number variation driven by tandem duplication. Demonstrating practical application of the genome sequence, we develop a targeted genotyping assay and use high-resolution genome-wide association analysis to dissect the genetic basis of seed size and hilum colour. The resources presented constitute a genomics-based breeding platform for faba bean, enabling breeders and geneticists to accelerate the improvement of sustainable protein production across the Mediterranean, subtropical and northern temperate agroecological zones.


Subject(s)
Crops, Agricultural , Diploidy , Genetic Variation , Genome, Plant , Genomics , Plant Breeding , Plant Proteins , Vicia faba , Chromosomes, Plant/genetics , Crops, Agricultural/genetics , Crops, Agricultural/metabolism , DNA Copy Number Variations/genetics , DNA, Satellite/genetics , Gene Amplification/genetics , Genes, Plant/genetics , Genetic Variation/genetics , Genome, Plant/genetics , Genome-Wide Association Study , Geography , Plant Breeding/methods , Plant Proteins/genetics , Plant Proteins/metabolism , Recombination, Genetic , Retroelements/genetics , Seeds/anatomy & histology , Seeds/genetics , Vicia faba/anatomy & histology , Vicia faba/genetics , Vicia faba/metabolism
2.
Proc Natl Acad Sci U S A ; 121(7): e2313789121, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38335257

ABSTRACT

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.


Subject(s)
Chiroptera , Filoviridae , Animals , Phylogeny , China , Mammals
3.
PLoS Biol ; 21(1): e3001958, 2023 01.
Article in English | MEDLINE | ID: mdl-36603052

ABSTRACT

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.


Subject(s)
Ganglia, Spinal , Nociception , Rats , Mice , Animals , Rats, Sprague-Dawley , Ganglia, Spinal/physiology , Central Nervous System , Pain , gamma-Aminobutyric Acid
4.
J Neurosci ; 44(11)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38267258

ABSTRACT

Phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), play a crucial role in controlling key cellular functions such as membrane and vesicle trafficking, ion channel, and transporter activity. Phosphatidylinositol 4-kinases (PI4K) are essential enzymes in regulating the turnover of phosphoinositides. However, the functional role of PI4Ks and mediated phosphoinositide metabolism in the central nervous system has not been fully revealed. In this study, we demonstrated that PI4KIIIß, one of the four members of PI4Ks, is an important regulator of VTA dopaminergic neuronal activity and related depression-like behavior of mice by controlling phosphoinositide turnover. Our findings provide new insights into possible mechanisms and potential drug targets for neuropsychiatric diseases, including depression. Both sexes were studied in basic behavior tests, but only male mice could be used in the social defeat depression model.


Subject(s)
Dopaminergic Neurons , Ventral Tegmental Area , Female , Mice , Male , Animals , Dopaminergic Neurons/physiology , Ventral Tegmental Area/physiology , Depression , Phosphatidylinositols/metabolism , Central Nervous System
5.
Am J Pathol ; 194(5): 656-672, 2024 May.
Article in English | MEDLINE | ID: mdl-38325552

ABSTRACT

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease for which there is no curative therapy available. Repetitive alveolar epithelial injury repair, myofibroblast accumulation, and excessive collagen deposition are key pathologic features of idiopathic pulmonary fibrosis, eventually leading to cellular hypoxia and respiratory failure. The precise mechanism driving this complex maladaptive process remains inadequately understood. WD repeat and suppressor of cytokine signaling box containing 1 (WSB1) is an E3 ubiquitin ligase, the expression of which is associated strongly with hypoxia, and forms a positive feedback loop with hypoxia-inducible factor 1α (HIF-1α) under anoxic condition. This study explored the expression, cellular distribution, and function of WSB1 in bleomycin (BLM)-induced mouse lung injury and fibrosis. WSB1 expression was highly induced by BLM injury and correlated with the progression of lung fibrosis. Significantly, conditional deletion of Wsb1 in adult mice ameliorated BLM-induced pulmonary fibrosis. Phenotypically, Wsb1-deficient mice showed reduced lipofibroblast to myofibroblast transition, but enhanced alveolar type 2 proliferation and differentiation into alveolar type 1 after BLM injury. Proteomic analysis of mouse lung tissues identified caveolin 2 as a potential downstream target of WSB1, contributing to BLM-induced epithelial injury repair and fibrosis. These findings unravel a vital role for WSB1 induction in lung injury repair, thus highlighting it as a potential therapeutic target for pulmonary fibrosis.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Injury , Animals , Mice , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Myofibroblasts/metabolism , Lung Injury/pathology , Proteomics , Lung/pathology , Fibrosis , Hypoxia/pathology , Idiopathic Pulmonary Fibrosis/pathology , Bleomycin/toxicity , Regeneration , Intracellular Signaling Peptides and Proteins
6.
FASEB J ; 38(10): e23661, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38733310

ABSTRACT

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.


Subject(s)
Fibroblast Growth Factors , Mice, Knockout , Microtubules , Pruritus , TRPV Cation Channels , Animals , Humans , Male , Mice , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/genetics , Ganglia, Spinal/metabolism , HEK293 Cells , Mice, Inbred C57BL , Microtubules/metabolism , Pruritus/metabolism , Pruritus/genetics , TRPA1 Cation Channel/metabolism , TRPA1 Cation Channel/genetics , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics
7.
J Cell Mol Med ; 28(1): e18028, 2024 01.
Article in English | MEDLINE | ID: mdl-37985436

ABSTRACT

Pathological cardiac hypertrophy is a key contributor to heart failure, and the molecular mechanisms underlying honokiol (HNK)-mediated cardioprotection against this condition remain worth further exploring. This study aims to investigate the effect of HNK on angiotensin II (Ang II)-induced myocardial hypertrophy and elucidate the underlying mechanisms. Sprague-Dawley rats were exposed to Ang II infusion, followed by HNK or vehicle treatment for 4 weeks. Our results showed that HNK treatment protected against Ang II-induced myocardial hypertrophy, fibrosis and dysfunction in vivo and inhibited Ang II-induced hypertrophy in neonatal rat ventricular myocytes in vitro. Mechanistically, HNK suppressed the Ang II-induced Nur77 expression at the transcriptional level and promoted ubiquitination-mediated degradation of Nur77, leading to dissociation of the Nur77-LKB1 complex. This facilitated the translocation of LKB1 into the cytoplasm and activated the LKB1-AMPK pathway. Our findings suggest that HNK attenuates pathological remodelling and cardiac dysfunction induced by Ang II by promoting dissociation of the Nur77-LKB1 complex and subsequent activation of AMPK signalling. This study uncovers a novel role of HNK on the LKB1-AMPK pathway to protect against cardiac hypertrophy.


Subject(s)
AMP-Activated Protein Kinases , Allyl Compounds , Angiotensin II , Biphenyl Compounds , Phenols , Rats , Animals , Angiotensin II/metabolism , AMP-Activated Protein Kinases/metabolism , Rats, Sprague-Dawley , Cardiomegaly/metabolism , Myocytes, Cardiac/metabolism
8.
Anal Chem ; 96(24): 9817-9825, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38730304

ABSTRACT

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.


Subject(s)
Biosensing Techniques , Breath Tests , Gram-Positive Bacteria , Peptidoglycan , Peptidoglycan/analysis , Peptidoglycan/chemistry , Breath Tests/methods , Gram-Positive Bacteria/isolation & purification , Humans , Limit of Detection , Aptamers, Nucleotide/chemistry
9.
Mol Carcinog ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860604

ABSTRACT

The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.

10.
BMC Cancer ; 24(1): 270, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38408977

ABSTRACT

BACKGROUND: Previous studies have observed a link between immunophenotypes and lung cancer, both of which are closely associated with genetic factors. However, the causal relationship between them remains unclear. METHODS: Bidirectional Mendelian randomization (MR) was performed on publicly available genome-wide association study (GWAS) summary statistics to analyze the causal relationships between 731 immunophenotypes and lung cancer. Sensitivity analyses were conducted to verify the robustness, heterogeneity, and potential horizontal pleiotropy of our findings. RESULTS: Following Bonferroni adjustment, CD14- CD16+ monocyte (OR = 0.930, 95%CI 0.900-0.960, P = 8.648 × 10- 6, PBonferroni = 0.006) and CD27 on CD24+ CD27+ B cells (OR = 1.036, 95%CI 1.020-1.053, P = 1.595 × 10 - 5, PBonferroni = 0.012) were identified as having a causal role in lung cancer via the inverse variance weighted (IVW) method. At a more relaxed threshold, CD27 on IgD+ CD24+ B cell (OR = 1.035, 95%CI 1.017-1.053, P = 8.666 × 10- 5, PBonferroni = 0.063) and CD27 on switched memory B cell (OR = 1.037, 95%CI 1.018-1.056, P = 1.154 × 10- 4, PBonferroni = 0.084) were further identified. No statistically significant effects of lung cancer on immunophenotypes were found. CONCLUSIONS: The elevated level of CD14- CD16+ monocytes was a protective factor against lung cancer. Conversely, CD27 on CD24+ CD27+ B cell was a risk factor. CD27 on class-switched memory B cells and IgD+ CD24+ B cells were potential risk factors for lung cancer. This research enhanced our comprehension of the interplay between immune responses and lung cancer risk. Additionally, these findings offer valuable perspectives for the development of immunologically oriented therapeutic strategies.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Causality , Risk Factors
11.
Eur J Pediatr ; 183(3): 1315-1323, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38117354

ABSTRACT

Severe adenoviral pneumonia (SAP) can cause post-infectious bronchiolitis obliterans (PIBO) in children. We aimed to investigate the relevant risk factors for PIBO and develop a predictive nomogram for PIBO in children with SAP. This prospective study analysed the clinical data of hospitalised children with SAP and categorised them into the PIBO and non-PIBO groups. Least absolute shrinkage and selection operator (LASSO) regressions were applied to variables that exhibited significant intergroup differences. Logistic regression was adopted to analyse the risk factors for PIBO. Additionally, a nomogram was constructed, and its effectiveness was assessed using calibration curves, C-index, and decision curve analysis. A total of 148 hospitalised children with SAP were collected in this study. Among them, 112 achieved favourable recovery, whereas 36 developed PIBO. Multivariable regression after variable selection via LASSO revealed that aged < 1 year (OR, 2.38, 95% CI, 0.82-6.77), admission to PICU (OR, 24.40, 95% CI, 7.16-105.00), long duration of fever (OR, 1.16, 95% CI, 1.04-1.31), and bilateral lung infection (OR, 8.78, 95% CI, 1.32-195.00) were major risk factors for PIBO. The nomogram model included the four risk factors: The C-index of the model was 0.85 (95% CI, 0.71-0.99), and the area under the curve was 0.85 (95% CI, 0.78-0.92). The model showed good calibration with the Hosmer-Lemeshow test (χ2 = 8.52, P = 0.38) and was useful in clinical settings with decision curve analysis. CONCLUSION: Age < 1 year, PICU admission, long fever duration, and bilateral lung infection are independent risk factors for PIBO in children with SAP. The nomogram model may aid clinicians in the early diagnosis and intervention of PIBO. WHAT IS KNOWN: • Adenoviruses are the most common pathogens associated with PIBO. • Wheezing, tachypnoea, hypoxemia, and mechanical ventilation are the risk factors for PIBO. WHAT IS NEW: • Age < 1 year, admission to PICU, long duration of fever days, and bilateral lung infection are independent risk factors for PIBO in children with SAP. • A prediction model presented as a nomogram may help clinicians in the early diagnosis and intervention of PIBO.


Subject(s)
Bronchiolitis Obliterans , Pneumonia, Viral , Child , Humans , Prospective Studies , Bronchiolitis Obliterans/diagnosis , Bronchiolitis Obliterans/etiology , Pneumonia, Viral/complications , Risk Factors
12.
World J Surg Oncol ; 22(1): 154, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38862958

ABSTRACT

BACKGROUND: Few studies have explored the impact of preoperative frailty on infectious complications in patients with a diagnosis of colorectal cancer (CRC). Therefore, this study aimed to investigate the effect of preoperative frailty on postoperative infectious complications and prognosis in patients with CRC using propensity score matching (PSM). METHODS: This prospective single-centre observational cohort study included 245 patients who underwent CRC surgery at the Department of Gastrointestinal Surgery, The Affiliated Lianyungang Hospital of Xuzhou Medical University between August 2021 to May 2023. Patients were categorised into two groups: frail and non-frail. They were matched for confounders and 1:1 closest matching was performed using PSM. Rates of infectious complications, intensive care unit (ICU) admission, 30-day mortality, and 90-day mortality, as well as postoperative length of hospital stay, total length of hospital stay, and hospital costs, were compared between the two groups. Binary logistic regression using data following PSM to explore independent factors for relevant outcome measures. RESULTS: After PSM, each confounding factor was evenly distributed between groups, and 75 pairs of patients were successfully matched. The incidence of intra-abdominal infectious complications was significantly higher in the frail group than in the non-frail group (10.7% vs. 1.3%, P < 0.05). There were no significant differences in ICU admission rate, postoperative length of hospital stay, total length of hospital stay, hospital costs, 30-day mortality rate, or 90-day mortality rate between the two groups (P > 0.05). Our logistic regression analysis result showed that preoperative frailty (OR = 12.014; 95% CI: 1.334-108.197; P = 0.027) was an independent factor for intra-abdominal infection. CONCLUSIONS: The presence of preoperative frailty elevated the risk of postoperative intra-abdominal infectious complications in patients undergoing CRC surgery. Therefore, medical staff should assess preoperative frailty in patients with CRC early and provide targeted prehabilitation interventions.


Subject(s)
Colorectal Neoplasms , Frailty , Postoperative Complications , Propensity Score , Humans , Male , Female , Colorectal Neoplasms/surgery , Colorectal Neoplasms/complications , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Prospective Studies , Prognosis , Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Middle Aged , Frailty/complications , Frailty/epidemiology , Follow-Up Studies , Length of Stay/statistics & numerical data , Risk Factors , Survival Rate , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Incidence
13.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Article in English | MEDLINE | ID: mdl-33753478

ABSTRACT

Species in a shared environment tend to evolve similar adaptations under the influence of their phylogenetic context. Using snowfinches, a monophyletic group of passerine birds (Passeridae), we study the relative roles of ancestral and species-specific adaptations to an extreme high-elevation environment, the Qinghai-Tibet Plateau. Our ancestral trait reconstruction shows that the ancestral snowfinch occupied high elevations and had a larger body mass than most nonsnowfinches in Passeridae. Subsequently, this phenotypic adaptation diversified in the descendant species. By comparing high-quality genomes from representatives of the three phylogenetic lineages, we find that about 95% of genes under positive selection in the descendant species are different from those in the ancestor. Consistently, the biological functions enriched for these species differ from those of their ancestor to various degrees (semantic similarity values ranging from 0.27 to 0.5), suggesting that the three descendant species have evolved divergently from the initial adaptation in their common ancestor. Using a functional assay to a highly selective gene, DTL, we demonstrate that the nonsynonymous substitutions in the ancestor and descendant species have improved the repair capacity of ultraviolet-induced DNA damage. The repair kinetics of the DTL gene shows a twofold to fourfold variation across the ancestor and the descendants. Collectively, this study reveals an exceptional case of adaptive evolution to high-elevation environments, an evolutionary process with an initial adaptation in the common ancestor followed by adaptive diversification of the descendant species.


Subject(s)
Acclimatization/genetics , Body Size/genetics , Mutation Rate , Selection, Genetic , Altitude , Amino Acid Substitution , Animals , DNA Repair , Nuclear Proteins/genetics , Phylogeny , Species Specificity , Tibet
14.
Aesthetic Plast Surg ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862659

ABSTRACT

BACKGROUND: Nipple-areola complex (NAC) necrosis is a major complication for breast reconstruction after nipple-sparing mastectomy. Although intraoperative indocyanine green angiography helps to assess the viability of tissue, the imaging could be conservative which may lead to aggressive resection. The plastic surgeons are eager to know the perfusion changes of NAC throughout the perioperative period. METHODS: In this prospective cohort study, the authors enrolled patients who underwent NSM and immediate direct-to-implant breast reconstruction. All patients underwent laser speckle contrast imaging before surgery, immediately after mastectomy, after implant placement, and 24 h and 72 h after surgery. RESULTS: A total of 94 breasts were analyzed, including 64 breasts healed with viable NAC and 30 breasts with NAC necrosis. In viable NACs, the average blood supply decreased to 56% after NSM and 42% after reconstruction, then recovered to 68% and 80% at 24-h and 72-h post-operation. In necrotic NACs, the average blood supply decreased to 33% after NSM and 24% after reconstruction, and partial perfusion recovery was also recorded at 24-h (31%) and 72-h (37%) post-operation. The cutoff value for predicting NAC viability is 40% after NSM and 25% after implant placement. CONCLUSIONS: The study quantified the NAC perfusion changes during the perioperative period. NAC perfusion decreased significantly after NSM and would be the lowest after the end of breast reconstruction. Viable NACs displayed more perfusion during the operation and showed significant nipple revascularization after breast reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

15.
J Environ Manage ; 361: 121270, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38820796

ABSTRACT

Reliable nitrogen (N) fertilizer management indicators are essential for improving crop yields and minimizing environmental impacts for sustainable production. The objectives of this study were to assess the importance of major N management indicators (NMIs) for higher yield with low risks of environmental pollution in an intensive potato system under drip irrigation. Six drip-irrigated field experiments with no N application (Control), farmer practice (FP), and optimized N management (OM) based on N-balance, soil mineral N (Nmin), and target yield were conducted from 2018 to 2020 in Inner Mongolia, China. The response of NMIs to potato yield and yield-based environment impact indices (EIY) was evaluated by the random forest algorithm. The N input, N losses from N leaching, ammonia (NH3) volatilization, nitrous oxide (N2O) emission, N use efficiency (NUE), N surplus, and soil residual N after harvest were obtained to identify the best NMIs for high yield and minimal ecological impact. The N management practices in field experimental sites affected the importance of the order of NMIs on potato yield and EIY. The NUE and N leaching were identified as the highest importance scores and the most essential controlling variables to potato yield and EIY, respectively. The integrated NUE and N leaching indicator played a vital role in improving potato yield and reducing ecological impact. The OM treatment achieved 46.0%, 63.6%, and 64.6% lower in N application rate, N surplus, and reactive N loss, and 62.4% higher in NUE than the FP treatment while achieving equal potato yields, respectively. Those key NMIs can guide farmers in understanding their practice short comes to achieve both high productivity and environmental sustainability in intensive potato production systems under drip irrigation.


Subject(s)
Agricultural Irrigation , Crop Production , Fertilizers , Nitrogen , Soil , Solanum tuberosum , Solanum tuberosum/growth & development , Agricultural Irrigation/methods , Crop Production/methods , Soil/chemistry , China , Agriculture/methods , Crops, Agricultural/growth & development
16.
BMC Oral Health ; 24(1): 411, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38575895

ABSTRACT

BACKGROUND: The oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression. METHODS: In this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups. RESULTS: The results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to  that in plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer. CONCLUSIONS: Significant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.


Subject(s)
Dental Plaque , Mouth Neoplasms , Humans , Saliva/microbiology , Dental Plaque/microbiology , Bacteria/genetics , RNA, Ribosomal, 16S/genetics
17.
J Biol Chem ; 298(3): 101731, 2022 03.
Article in English | MEDLINE | ID: mdl-35176281

ABSTRACT

Lung cancer has the highest mortality among cancers worldwide due to its high incidence and lack of the effective cures. We have previously demonstrated that the membrane ion channel TMEM16A is a potential drug target for the treatment of lung adenocarcinoma and have identified a pocket of inhibitor binding that provides the basis for screening promising new inhibitors. However, conventional drug discovery strategies are lengthy and costly, and the unpredictable side effects lead to a high failure rate in drug development. Therefore, finding new therapeutic directions for already marketed drugs may be a feasible strategy to obtain safe and effective therapeutic drugs. Here, we screened a library of over 1400 Food and Drug Administration-approved drugs through virtual screening and activity testing. We identified a drug candidate, Zafirlukast (ZAF), clinically approved for the treatment of asthma, that could inhibit the TMEM16A channel in a concentration-dependent manner. Molecular dynamics simulations and site-directed mutagenesis experiments showed that ZAF can bind to S387/N533/R535 in the nonselective inhibitor binding pocket, thereby blocking the channel pore. Furthermore, we demonstrate ZAF can target TMEM16A channel to inhibit the proliferation and migration of lung adenocarcinoma LA795 cells. In vivo experiments showed that ZAF can significantly inhibit lung adenocarcinoma tumor growth in mice. Taken together, we identified ZAF as a novel TMEM16A channel inhibitor with excellent anticancer activity, and as such, it represents a promising candidate for future preclinical and clinical studies.


Subject(s)
Adenocarcinoma of Lung , Anoctamin-1 , Indoles , Lung Neoplasms , Phenylcarbamates , Sulfonamides , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Animals , Anoctamin-1/antagonists & inhibitors , Anoctamin-1/metabolism , Chloride Channels , Indoles/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mice , Phenylcarbamates/pharmacology , Sulfonamides/pharmacology
18.
BMC Genomics ; 24(1): 203, 2023 Apr 17.
Article in English | MEDLINE | ID: mdl-37069497

ABSTRACT

The freshwater leech Whitmania pigra (W. pigra) Whitman (Annelida phylum) is a model organism for neurodevelopmental studies. However, molecular biology research on its embryonic development is still scarce. Here, we described a series of developmental stages of the W. pigra embryos and defined five broad stages of embryogenesis: cleavage stages, blastocyst stage, gastrula stage, organogenesis and refinement, juvenile. We obtained a total of 239.64 Gb transcriptome data of eight representative developmental phases of embryos (from blastocyst stage to maturity), which was then assembled into 21,482 unigenes according to our reference genome sequenced by single-molecule real-time (SMRT) long-read sequencing. We found 3114 genes differentially expressed during the eight phases with phase-specific expression pattern. Using a comprehensive transcriptome dataset, we demonstrated that 57, 49 and 77 DEGs were respectively related to morphogenesis, signal pathways and neurogenesis. 49 DEGs related to signal pathways included 30 wnt genes, 14 notch genes, and 5 hedgehog genes. In particular, we found a cluster consisting of 7 genes related to signal pathways as well as synapses, which were essential for regulating embryonic development. Eight genes cooperatively participated in regulating neurogenesis. Our results reveal the whole picture of W. pigra development mechanism from the perspective of transcriptome and provide new clues for organogenesis and neurodevelopmental studies of Annelida species.


Subject(s)
Hedgehog Proteins , Leeches , Animals , Fresh Water , Gene Expression Profiling , Hedgehog Proteins/genetics , Leeches/genetics , Leeches/growth & development , Neurogenesis , Transcriptome , Embryo, Nonmammalian/metabolism
19.
Opt Express ; 31(23): 38365-38375, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-38017944

ABSTRACT

Backward stimulated Brillouin scattering (SBS) in optical microcavities has been widely used in nonlinear optics and microwave photonics. Compared with glass material microcavity, magnesium fluoride crystal microcavity has the advantages of small absorption coefficient, fewer defects and larger nonlinear coefficient, moreover, it usually has a narrow gain bandwidth of tens of megahertz. Here, we design a high precision machining system to produce ultra-smooth surface magnesium fluoride crystal disk cavities with a diameter of about 5 mm, Q value exceeding 108, FSR matching material Brillouin gain. By simply modulating the pump wavelength and coupling power, we observe SBS phenomena with a 13.47 GHz Brillouin frequency shift near 1.55µm and cascaded stimulated Brillouin lasers (SBL) of up to 12 orders. In addition, the Brillouin-Kerr optical frequency comb in this device is demonstrated, observing nearly 300 comb lines spanning across a spectral window of 250 nm. Our research provides a way to fabricate high-Q crystal microcavities and demonstrates the potential of these devices in applications such as microwave sources and nonlinear optics.

20.
Glob Chang Biol ; 29(13): 3575-3590, 2023 07.
Article in English | MEDLINE | ID: mdl-37021594

ABSTRACT

Enhancing soil organic carbon (SOC) sequestration and food supply are vital for human survival when facing climate change. Site-specific best management practices (BMPs) are being promoted for adoption globally as solutions. However, how SOC and crop yield are related to each other in responding to BMPs remains unknown. Here, path analysis based on meta-analysis and machine learning was conducted to identify the effects and potential mechanisms of how the relationship between SOC and crop yield responds to site-specific BMPs in China. The results showed that BMPs could significantly enhance SOC and maintain or increase crop yield. The maximum benefits in SOC (30.6%) and crop yield (79.8%) occurred in mineral fertilizer combined with organic inputs (MOF). Specifically, the optimal SOC and crop yield would be achieved when the areas were arid, soil pH was ≥7.3, initial SOC content was ≤10 g kg-1 , duration was >10 years, and the nitrogen (N) input level was 100-200 kg ha-1 . Further analysis revealed that the original SOC level and crop yield change showed an inverted V-shaped structure. The association between the changes in SOC and crop yield might be linked to the positive role of the nutrient-mediated effect. The results generally suggested that improving the SOC can strongly support better crop performance. Limitations in increasing crop yield still exist due to low original SOC level, and in regions where the excessive N inputs, inappropriate tillage or organic input is inadequate and could be diminished by optimizing BMPs in harmony with site-specific conditions.


Subject(s)
Agriculture , Soil , Humans , Soil/chemistry , Agriculture/methods , Carbon/analysis , Carbon Sequestration , China , Crops, Agricultural
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