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1.
Nucleic Acids Res ; 52(D1): D285-D292, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37897340

ABSTRACT

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.


Subject(s)
Chromatin Immunoprecipitation Sequencing , Chromatin , Databases, Genetic , Single-Cell Analysis , Chromatin/genetics , Epigenesis, Genetic , Humans , Animals
2.
BMC Genomics ; 25(1): 578, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858635

ABSTRACT

BACKGROUND: Rose myrtle (Rhodomyrtus tomentosa (Ait.) Hassk), is an evergreen shrub species belonging to the family Myrtaceae, which is enriched with bioactive volatiles (α-pinene and ß-caryophyllene) with medicinal and industrial applications. However, the mechanism underlying the volatile accumulation in the rose myrtle is still unclear. RESULTS: Here, we present a chromosome-level genomic assembly of rose myrtle (genome size = 466 Mb, scaffold N50 = 43.7 Mb) with 35,554 protein-coding genes predicted. Through comparative genomic analysis, we found that gene expansion and duplication had a potential contribution to the accumulation of volatile substances. We proposed that the action of positive selection was significantly involved in volatile accumulation. We identified 43 TPS genes in R. tomentosa. Further transcriptomic and TPS gene family analyses demonstrated that the distinct gene subgroups of TPS may contribute greatly to the biosynthesis and accumulation of different volatiles in the Myrtle family of shrubs and trees. The results suggested that the diversity of TPS-a subgroups led to the accumulation of special sesquiterpenes in different plants of the Myrtaceae family. CONCLUSIONS: The high quality chromosome-level rose myrtle genome and the comparative analysis of TPS gene family open new avenues for obtaining a higher commercial value of essential oils in medical plants.


Subject(s)
Chromosomes, Plant , Evolution, Molecular , Genome, Plant , Genomics , Myrtaceae , Terpenes , Terpenes/metabolism , Genomics/methods , Myrtaceae/genetics , Myrtaceae/metabolism , Chromosomes, Plant/genetics , Phylogeny , Multigene Family
3.
BMC Genomics ; 25(1): 92, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254015

ABSTRACT

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.


Subject(s)
Antelopes , Animals , Antelopes/genetics , Phylogeny , Goats/genetics , Gene Rearrangement , Chromosomes
4.
J Am Chem Soc ; 146(5): 2928-2932, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38289153

ABSTRACT

The asymmetric total synthesis of pedrolide (>200 mg) with an unprecedented [5-5-5-6-6-3] hexacyclic core (pedrolane) was achieved. Its unique bicyclo[2.2.1]heptane ring system was efficiently constructed via an enantioselective ene reaction of cyclopentadiene followed by a Wittig reaction, isomerization, and a diastereoselective intramolecular Diels-Alder reaction cascade. The highly oxygenated carane [6-3] ring system was synthesized via a ring-closing metathesis reaction followed by an unusual free carbene cyclopropanation. Furthermore, the 12 contiguous stereocenters of pedrolide were installed diastereoselectively.

5.
Plant Physiol ; 192(3): 1836-1857, 2023 07 03.
Article in English | MEDLINE | ID: mdl-36805285

ABSTRACT

Drought stress substantially reduces the productivity of apple plants and severely restricts the development of apple industry. Malus sieversii, wild apples with excellent drought resistance, is a valuable wild resource for a rootstock improvement of cultivated apple (Malus domestica). miRNAs and their targets play essential roles in plant growth and stress responses, but their roles in drought stress responses in apple are unknown. Here, we demonstrate that microRNA156ab is upregulated in M. sieversii in response to drought stress. Overexpressing msi-miR156ab promoted auxin accumulation, maintained the growth of apple plants, and increased plant resistance to osmotic stress. Antioxidant enzyme activities and proline contents were also increased in miR156ab-OE transgenic apple lines, which improved drought resistance. The squamosa promoter binding protein-like transcription factor MsSPL13 is the target of msi-miR156ab, as demonstrated by 5'-RACE and dual luciferase assays. Heterologous expression of MsSPL13 decreased auxin contents and inhibited growth in Arabidopsis (Arabidopsis thaliana) under normal and stress conditions. The activities of antioxidant enzymes were also suppressed in MsSPL13-OE transgenic Arabidopsis, reducing drought resistance. We showed that MsSPL13 regulates the expression of the auxin-related genes MsYUCCA5, PIN-FORMED7 (MsPIN7), and Gretchen Hagen3-5 (MsGH3-5) by binding to the GTAC cis-elements in their promoters, thereby regulating auxin metabolism. Finally, we demonstrated that the miR156ab-SPL13 module is involved in mediating the difference in auxin metabolism and stress responses between M. sieversii and M26 (M. domestica) rootstocks. Overall, these findings reveal that the miR156ab-SPL13 module enhances drought stress tolerance in apples by regulating auxin metabolism and antioxidant enzyme activities.


Subject(s)
Arabidopsis , Malus , Malus/metabolism , Drought Resistance , Transcription Factors/genetics , Transcription Factors/metabolism , Antioxidants/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Gene Expression Regulation, Plant , Droughts , Indoleacetic Acids/metabolism , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/metabolism
6.
Pediatr Res ; 95(4): 1041-1050, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38040988

ABSTRACT

BACKGROUNDS: This study aimed to identify risk factors for the progression of coronary artery lesions (CALs) in children with Kawasaki disease (KD) and to develop a nomogram prediction model. METHODS: This is a retrospective case-control study in which the participants were categorized into three groups based on the changes of the maximum Z score (Zmax) of coronary arteries at the 1-month follow-up compared with the baseline Zmax: CALs-progressed, CALs-improved, and CALs-unchanged. RESULTS: Of total 387 patients, 65 (27%), 319 (73%), and 3 (0.7%) patients were categorized into CALs-progressed group, CALs-improved group, and CALs-unchanged group, respectively. Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, C-reactive protein, albumin, and soluble interleukin-2 receptor (odds ratio: 7.19, 1.51, 2.32, 1.52, 0.86, and 1.46, respectively; all P-values < 0.01). The nomogram prediction model including these six independent risk factors yielded an area under the curve (AUC) of 0.80 (95% confidence interval, 0.74 to 0.86). The accuracy of this model reached 81.7% after the Monte-Carlo Bootstrapping 1000 repetitions. CONCLUSIONS: The nomogram prediction model can identify children at high risk for the progression of CALs at early stages. IMPACT: Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, CRP, ALB, and sIL-2R. The prediction model we constructed can identify children at high risk for the progression of CALs at early stages and help clinicians make individualized treatment plans. Prospective, multi-centered studies with larger sample sizes are warranted to validate the power of this prediction model in children with KD.


Subject(s)
Coronary Artery Disease , Mucocutaneous Lymph Node Syndrome , Child , Humans , Infant , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Immunoglobulins, Intravenous , Coronary Vessels/diagnostic imaging , Retrospective Studies , Case-Control Studies , Prospective Studies , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/complications
7.
Exp Brain Res ; 242(2): 443-449, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38147087

ABSTRACT

The purpose of this study was to identify the target genes of tcon_00044595, elucidate its activation site, and provide novel insights into the pathogenesis and treatment of neonatal hypoxic-ischemic brain damage (HIBD). Through homologous blast analysis, we identified predicted target sequences in the neighboring regions of the long non-coding RNA (lncRNA) tcon_00044595, suggesting that limd1 is its target gene. Starbase was utilized to identify potential candidate microRNAs associated with the lncRNA. The interaction between the candidate microRNAs and limd1 was investigated and validated using various experimental methods including in vitro cell culture, cell transfection, dual fluorescence reporter detection system, and real-time PCR. Homology alignment analysis revealed that the lncRNA tcon_00044595 exhibited a 246 bp homologous sequence at the 3' end of the adjacent limd1 gene, with a conservation rate of 68%. Analysis conducted on Starbase online identified three potential microRNA candidates: miR-3471, miR-883a-5p, and miR-214-3p. Intracellular expression of the limd1 gene was significantly down-regulated upon transfection with miR-3471, while the other two microRNAs did not produce noticeable effects. Luciferase reporter assays identified two interaction sites (UTR-1, UTR-2) between miR-3471 and the limd1 3'UTR, with UTR-1 exhibiting a strong influence. Further CCK8 assay indicated a protective role of miR-3471 during low oxygen stroke in HIBD. The potential regulatory relationship between lncRNA (tcon_00044595), miR-3471, and the target gene limd1 suggests their involvement in the occurrence and development of HIBD, providing new insights for investigating the underlying mechanisms and exploring targeted therapeutic approaches for HIBD.


Subject(s)
Hypoxia-Ischemia, Brain , MicroRNAs , RNA, Long Noncoding , Humans , Infant, Newborn , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , MicroRNAs/genetics , Hypoxia-Ischemia, Brain/genetics , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/pathology , Apoptosis , Oxygen
8.
Acta Pharmacol Sin ; 45(9): 1809-1820, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38750074

ABSTRACT

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2 and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 µM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.


Subject(s)
Animals, Newborn , Hippocampus , Hypoxia-Ischemia, Brain , Mitophagy , Neurons , Rats, Sprague-Dawley , Animals , Male , Rats , Cell Survival/physiology , Cells, Cultured , Hippocampus/metabolism , Hippocampus/pathology , Hypoxia-Ischemia, Brain/metabolism , Membrane Proteins/metabolism , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Mitophagy/physiology , Neurons/metabolism , Reactive Oxygen Species/metabolism
9.
Cereb Cortex ; 33(13): 8312-8320, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37015899

ABSTRACT

Existing studies demonstrate that comprehenders can predict semantic information during language comprehension. Most evidence comes from a highly constraining context, in which a specific word is likely to be predicted. One question that has been investigated less is whether prediction can occur when prior context is less constraining for predicting specific words. Here, we aim to address this issue by examining the prediction of animacy features in low-constraining context, using electroencephalography (EEG), in combination with representational similarity analysis (RSA). In Chinese, a classifier follows a numeral and precedes a noun, and classifiers constrain animacy features of upcoming nouns. In the task, native Chinese Mandarin speakers were presented with either animate-constraining or inanimate-constraining classifiers followed by congruent or incongruent nouns. EEG amplitude analysis revealed an N400 effect for incongruent conditions, reflecting the difficulty of semantic integration when an incompatible noun is encountered. Critically, we quantified the similarity between patterns of neural activity following the classifiers. RSA results revealed that the similarity between patterns of neural activity following animate-constraining classifiers was greater than following inanimate-constraining classifiers, before the presentation of the nouns, reflecting pre-activation of animacy features of nouns. These findings provide evidence for the prediction of coarse-grained semantic feature of upcoming words.


Subject(s)
Comprehension , Electroencephalography , Language , Semantics , Female , Humans , Male , Comprehension/physiology , East Asian People , Evoked Potentials/physiology
10.
Cereb Cortex ; 33(15): 9367-9375, 2023 07 24.
Article in English | MEDLINE | ID: mdl-37317031

ABSTRACT

Do comprehenders predict the meaning and even the phonological form of upcoming words during language comprehension? With a growing body of evidence suggesting that semantic representations may be predicted, the evidence for phonological prediction is less clear and largely derived from studies conducted in languages utilizing an alphabetic script. In this research, we aim to examine the prediction of phonological information in the processing of Chinese idioms through the use of ERP representational similarity analysis (RSA). The study utilizes four-character Chinese idioms, and phonological overlap was manipulated by varying the syllable at the idiom-final part between idiom pairs so that pairs of idioms share a syllable (i.e. within-pairs) or not (between-pairs). We quantified the similarity between patterns of neural activity of idioms for within- and between-pairs. RSA results revealed greater similarity in neural activity patterns for idioms within-pairs, compared with between-pairs, and critically this similarity effect was observed prior to the presentation of the phonological similarity, providing evidence for the pre-activation of upcoming phonological information, under circumstances that encourage predictive processing.


Subject(s)
Comprehension , East Asian People , Humans , Comprehension/physiology , Language , Semantics , Asian People
11.
Ecotoxicol Environ Saf ; 284: 116903, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39205354

ABSTRACT

Ice, water, and sediment represent three interconnected habitats in lake ecosystems, and bacteria are crucial for maintaining ecosystem equilibrium and elemental cycling across these habitats. However, the differential characteristics and driving mechanisms of bacterial community structures in the ice, water, and sediments of seasonally frozen lakes remain unclear. In this study, high-throughput sequencing technology was used to analyze and compare the structure, function, network characteristics, and assembly mechanisms of bacterial communities in the ice, water, and sediment of Wuliangsuhai, a typical cold region in Inner Mongolia. The results showed that the bacterial communities in the ice and water phases had similar diversity and composition, with Proteobacteria, Bacteroidota, Actinobacteria, Campilobacterota, and Cyanobacteria as dominant phyla. The bacterial communities in sediments displayed significant differences from ice and water, with Chloroflexi, Proteobacteria, Firmicutes, Desulfobacterota, and Acidobacteriota being the dominant phyla. Notably, the bacterial communities in water exhibited higher spatial variability in their distribution than those in ice and sediment. This study also revealed that during the frozen period, the bacterial community species in the ice, water, and sediment media were dominated by cooperative relationships. Community assembly was primarily influenced by stochastic processes, with dispersal limitation and drift identified as the two most significant factors within this process. However, heterogeneous selection also played a significant role in the community composition. Furthermore, functions related to nitrogen, phosphorus, sulfur, carbon, and hydrogen cycling vary among bacterial communities in ice, water, and sediment. These findings elucidate the intrinsic mechanisms driving variability in bacterial community structure and changes in water quality across different media phases (ice, water, and sediment) in cold-zone lakes during the freezing period, offering new insights for water environmental protection and ecological restoration efforts in such environments.

12.
Int Orthop ; 48(7): 1743-1749, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38286924

ABSTRACT

PURPOSE: This study aimed to investigate the mid- to long-term benefits of high tibial osteotomy in advanced age patients. METHODS: This retrospective study was conducted in our hospital from January 2017 to January 2021 with data prospectively collected, 47 patients with knee osteoarthritis who over 65 years old were included, and a 1:1 propensity score (PS) of patients < 65 years were matched according to gender, body mass index, and side. Patient demographics, intraooperative and postoperative variables, and patient self-reported outcomes were compared. A generalized linear model was used to screen possible risk factors. RESULTS: A total of 94 consecutive patients were included; the average age of advanced age group was 69.47 + 4.26 years and 57.87 + 5.51 years in the younger group. There were no statistically difference in K-L grade, smoke, drink, comorbidity, ASA, blood loss, operative duration, length of stay, surgical site infection, hinge fracture, DVT, and preooperative and postoperative aFTA; significantly statistical difference of the eFI was found between two groups (P < 0.05). Two groups had comparable VAS and MOMAC scores at one year postoperatively (P > 0.05), while the younger group had lower VAS and WOMAC scores than the advanced age group at the end of follow-up (P < 0.05). Generalized linear model showed both age and eFI were associated with WOMAC scores; there was a statistically significant difference in the effect of eFI on WOMAC scores at different ages (P > 0.05). CONCLUSIONS: Compared with younger patients, advanced age patients have similar short-term benefits, but less long-term benefits. We recommend that patients proposed for HTO be discriminated by eFI, and patients with higher scores should be cautiously selected.


Subject(s)
Osteoarthritis, Knee , Osteotomy , Patient Reported Outcome Measures , Tibia , Humans , Male , Female , Aged , Osteoarthritis, Knee/surgery , Retrospective Studies , Osteotomy/methods , Osteotomy/adverse effects , Middle Aged , Tibia/surgery , Self Report , Age Factors , Treatment Outcome
13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 220-235, 2024 Feb 28.
Article in English, Zh | MEDLINE | ID: mdl-38755718

ABSTRACT

OBJECTIVES: The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate, making it difficult to master. This study aims to provide a crucial model for transplantation immunology research by modifying and developing novel techniques for mouse kidney transplantation. METHODS: A total of 57 pairs of mice were used to establish and compare the modified and innovative surgical techniques for mouse kidney transplantation. Three different surgical models were established, including the abdominal suture technique for orthotopic kidney transplantation, the abdominal cuff technique for orthotopic kidney transplantation, and the cervical cuff technique for ectopic kidney transplantation. BALB/c or C57BL/6 male mice, aged 8 to 12 weeks and weighed 20 to 25 g with specified pathogen free-grade were served as the donor mice or the recipient mice. The surgical technique characteristics, key surgical times, complications, and pathological examination in the early postoperative period were summarized and compared. RESULTS: Three different surgical models of mouse kidney transplantation were successfully established. The comparison of warm ischemic time for the 3 groups of mice showed no statistical significance (P=0.510 4). The abdominal suture group had the shortest total operation time of the donor compared with the abdominal cuff group and the cervical cuff group [(18.3±3.6) min vs (26.2±4.7) min and (22.8±2.5) min; both P<0.000 1]. There was a significant difference in cold ischemia time among the 3 groups (all P<0.000 1), with (60.8±4.1) min in the cervical cuff group, (43.3±5.0) min in the abdominal suture group, and (88.8±6.7) min in the abdominal cuff group. Due to different anastomosis methods, the cervical cuff group had the shortest time [(17.6±2.7) min], whereas the abdominal cuff group had the longest time [(38.8±5.4) min]. The total operation time for the recipients showed significant differences (P<0.000 1), with the abdominal suture group having the shortest time [(44.0±6.9) min], followed by the cervical cuff group [(64.1±5.2) min], and the abdominal cuff group [(80.0±6.0) min] being the longest. In the 32 mice of the abdominal suture group, there were 6 with intraoperative bleeding, including 1 arterial intimal injury bleeding and 5 with bleeding after vessel opening. Six mice had ureteral complications, including ureteral bladder anastomotic stenosis, necrosis, and renal pelvis dilation. Two mice had postoperative abdominal infections. In the abdominal cuff group, there was no intraoperative bleeding, but 6 mice showed mild arterial stenosis and 5 showed venous stenosis, 4 arterial injury, 4 arterial thrombosis, and 2 ureteral complications. No postoperative infections occurred in the mice. In the cervical cuff group, no intraoperative bleeding, arterial intimal injury, arterial/venous stenosis, or thrombosis were found in 13 mice. Five mice had ureteral complications, including ureteral necrosis and infection, which were the main complications in the cervical cuff group. The renal function in mice of the 3 groups remained stable 7 days after surgery. Hematoxylin and eosin staining and periodic acid-Schiff staining showed no significant differences in terms of acute rejection among the 3 surgical methods (all P>0.05). CONCLUSIONS: All 3 surgical methods are able to successfully establish mouse kidney transplantation models, with no significant differences observed in the short-term graft survival and acute rejection. The modified abdominal suture technique and abdominal cuff technique have their respective advantages in research applications. The novel cervical cuff technique for ectopic kidney transplantation model is relatively simple to be prepared and causes less trauma to the mice, providing more options for studies involving xenotransplantation, secondary transplantation, and local lymphatic drainage. However, the difficulty in harvesting the donor kidney and the high incidence of ureteral infections need further validation in long-term survival. This study holds important reference value for choosing the type of mouse kidney transplantation model for different research needs.


Subject(s)
Kidney Transplantation , Mice, Inbred BALB C , Mice, Inbred C57BL , Animals , Mice , Kidney Transplantation/methods , Kidney Transplantation/adverse effects , Male , Models, Animal
14.
Angew Chem Int Ed Engl ; 63(4): e202315232, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38059757

ABSTRACT

General methods for the preparation of geminal bis(boronates) are of great interest due to their widespread applications in organic synthesis. While the terminal gem-diboron compounds are readily accessible, the construction of the sterically encumbered, internal analogues has remained a prominent challenge. Herein, we report a formal umpolung strategy to access these valuable building blocks. The readily available 1,1-diborylalkanes were first converted into the corresponding α-halogenated derivatives, which then serve as electrophilic components, undergoing a formal substitution with a diverse array of nucleophiles to form a series of C-C, C-O, C-S, and C-N bonds. This protocol features good tolerance to steric hindrance and a wide variety of functional groups and heterocycles. Notably, this strategy can also be extended to the synthesis of diaryl and terminal gem-diboron compounds, therefore providing a general approach to various types of geminal bis(boronates).

15.
Int J Cancer ; 153(6): 1172-1181, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37260277

ABSTRACT

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.


Subject(s)
COVID-19 , Uterine Cervical Neoplasms , Female , Humans , COVID-19/epidemiology , Pandemics , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/therapy , China/epidemiology , Hospitals, University
16.
Hum Brain Mapp ; 44(11): 4200-4210, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37227015

ABSTRACT

Subcallosal cingulate gyrus (SCG) is a target of deep brain stimulation (DBS) for treatment-resistant depression. However, previous randomized controlled trials report that approximately 42% of patients are responders to this therapy of last resort, and suboptimal targeting of SCG is a potential underlying factor to this unsatisfactory efficacy. Tractography has been proposed as a supplementary method to enhance targeting strategy. We performed a connectivity-based segmentation in the SCG region via probabilistic tractography in 100 healthy volunteers from the Human Connectome Project. The SCG voxels with maximum connectivity to brain regions implicated in depression, including Brodmann Area 10 (BA10), cingulate cortex, thalamus, and nucleus accumbens were identified, and the conjunctions were deemed as tractography-based targets. We then performed deterministic tractography using these targets in additional 100 volunteers to calculate streamline counts compassing to relevant brain regions and fibers. We also evaluated the intra- and inter-subject variance using test-retest dataset. Two tractography-based targets were identified. Tractography-based target-1 had the highest streamline counts to right BA10 and bilateral cingulate cortex, while tractography-based target-2 had the highest streamline counts to bilateral nucleus accumbens and uncinate fasciculus. The mean linear distance from individual tractography-based target to anatomy-based target was 3.2 ± 1.8 mm and 2.5 ± 1.4 mm in left and right hemispheres. The mean ± SD of targets between intra- and inter-subjects were 2.2 ± 1.2 and 2.9 ± 1.4 in left hemisphere, and 2.3 ± 1.4 and 3.1 ± 1.7 in right hemisphere, respectively. Individual heterogeneity as well as inherent variability from diffusion imaging should be taken into account during SCG-DBS target planning procedure.


Subject(s)
Connectome , Deep Brain Stimulation , Depressive Disorder, Treatment-Resistant , White Matter , Humans , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiology , Deep Brain Stimulation/methods , Depression , White Matter/diagnostic imaging , Depressive Disorder, Treatment-Resistant/diagnostic imaging , Depressive Disorder, Treatment-Resistant/therapy
17.
Biochem Biophys Res Commun ; 674: 170-182, 2023 09 24.
Article in English | MEDLINE | ID: mdl-37423037

ABSTRACT

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Animals , Mice , Glioblastoma/pathology , RNA Polymerase II/genetics , RNA Polymerase II/metabolism , Cell Proliferation/genetics , Brain Neoplasms/pathology , RNA, Small Interfering/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic
18.
BMC Plant Biol ; 23(1): 259, 2023 May 16.
Article in English | MEDLINE | ID: mdl-37189063

ABSTRACT

BACKGROUND: Human-guided crop domestication has lasted for more than 10,000 years. In terms of the domestication and breeding of vegetables, cellulose content in edible tissues is one of the most important traits. Primulina eburnea is a recently developed calcium-rich vegetable with a high soluble and bioavailable calcium content in its leaves. However, the high cellulose content in the leaves hampers the taste, and no research has been reported on the genetic basis of cellulose biosynthesis in this calcium-rich vegetable. RESULTS: We identified 36 cellulose biosynthesis-involved genes belonging to eight gene families in the P. eburnea genome. The cellulose accumulated decreasingly throughout leaf development. Nineteen genes were considered core genes in cellulose biosynthesis, which were highly expressed in buds but lowly expressed in mature leaves. In the nitrogen fertilization experiment, exogenous nitrogen decreased the cellulose content in the buds. The expressing pattern of 14 genes were consistent with phenotypic variation in the nitrogen fertilization experiment, and thus they were proposed as cellulose toolbox genes. CONCLUSIONS: The present study provides a strong basis for the subsequent functional research of cellulose biosynthesis-involved genes in P. eburnea, and provides a reference for breeding and/or engineering this calcium-rich vegetable with decreased leaf cellulose content to improve the taste.


Subject(s)
Calcium , Cellulose , Humans , Vegetables , Plant Breeding , Nitrogen
19.
Plant Physiol ; 190(4): 2501-2518, 2022 11 28.
Article in English | MEDLINE | ID: mdl-36130298

ABSTRACT

Softening is a key step during fruit ripening that is modulated by the interplay between multiple phytohormones. The antagonistic action of abscisic acid (ABA) and auxin determines the rate of fruit ripening and softening. However, the transcription factors that integrate ABA and auxin signals to regulate fruit softening remain to be determined. In this study, we identified several DNA-binding with One Finger (Dof) transcription factors essential for ABA-promoted fruit softening, based on transcriptome analysis of two sweet cherry (Prunus avium L.) varieties with different fruit firmness. We show that PavDof6 directly binds to the promoters of genes encoding cell wall-modifying enzymes to activate their transcription, while PavDof2/15 directly repress their transcription. Transient overexpression of PavDof6 and PavDof2/15 in sweet cherry fruits resulted in precocious and delayed softening, respectively. In addition, we show that the auxin response factor PavARF8, the expression of whose encoding gene is repressed by ABA, activates PavDof2/15 transcription. Furthermore, PavDof2/6/15 and PavARF8 directly bind to the 9-cis-epoxycarotenoid dioxygenase 1 (PavNCED1) promoter and regulate its expression, forming a feedback mechanism for ABA-mediated fruit softening. These findings unveil the physiological framework of fruit softening and establish a direct functional link between the ABA-PavARF8-PavDofs module and cell-wall-modifying genes in mediating fruit softening.


Subject(s)
Abscisic Acid , Prunus avium , Abscisic Acid/pharmacology , Abscisic Acid/metabolism , Prunus avium/genetics , Fruit/metabolism , Gene Expression Regulation, Plant , Indoleacetic Acids/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
20.
Plasmid ; 125: 102670, 2023.
Article in English | MEDLINE | ID: mdl-36828204

ABSTRACT

The effective utilization of traditional Chinese medicine (TCM) has been challenged by the difficulty to accurately distinguish between similar plant varieties. The stability and conservation of the chloroplast genome can aid in resolving genotypes. Previous studies using nuclear sequences and molecular markers have not effectively differentiated the species from related taxa, such as Machilus leptophylla, Hanceola exserta, Rubus bambusarum, and Rubus henryi. This study aimed to characterize the chloroplast genomes of these four plant species, and analyze their simple sequence repeats (SSRs) and phylogenetic positions. The results demonstrated the four chloroplast genomes consisted of 152.624 kb, 153.296 kb, 156.309 kb, and 158.953 kb in length, involving 124, 130, 129, and 131 genes, respectively. They also contained four specific regions with mononucleotide being the class with the most members. Moreover, these repeating types of SSR were various in individual class. Phylogenetic analysis showed that M. leptophylla was clustered with M. yunnanensis, and H. exserta was confirmed as belonging to the family Ocimeae. Additionally, R. bambusarum and R. henryi were grouped together but differed in their SSR features, indicating that they were not the same species. This research provides evidence for resolving species and contributes new genetic information for further studies.


Subject(s)
Genome, Chloroplast , Phylogeny , Plasmids
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