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1.
BMC Genomics ; 25(1): 356, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600443

RESUMEN

BACKGROUND: Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown. RESULTS: We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions. CONCLUSIONS: This study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.


Asunto(s)
Chlorella , Humanos , Chlorella/genética , Centrómero/genética , Plantas/genética , Elementos Transponibles de ADN , Telómero/genética
2.
BMC Genomics ; 25(1): 354, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594645

RESUMEN

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.


Asunto(s)
Actinidia , Proteínas de Homeodominio , Proteínas de Homeodominio/genética , Genoma de Planta , Filogenia , Actinidia/genética , Leucina Zippers/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Perfilación de la Expresión Génica
3.
J Hepatol ; 80(6): 928-940, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38336346

RESUMEN

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.


Asunto(s)
Células Estrelladas Hepáticas , Hepatocitos , Cirrosis Hepática , Ratones Noqueados , Proteína de la Región Y Determinante del Sexo , Animales , Masculino , Femenino , Ratones , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/fisiopatología , Humanos , Hepatocitos/metabolismo , Proteína de la Región Y Determinante del Sexo/genética , Proteína de la Región Y Determinante del Sexo/metabolismo , Células Estrelladas Hepáticas/metabolismo , Caracteres Sexuales , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Tetracloruro de Carbono/toxicidad , Tetracloruro de Carbono/efectos adversos , Colestasis/genética , Colestasis/metabolismo , Colestasis/fisiopatología , Modelos Animales de Enfermedad
4.
Anal Chem ; 96(23): 9585-9592, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38816678

RESUMEN

The PD-L1 protein on extracellular vesicles (EVs) is a promising biomarker for tumor immunotherapy. However, PD-L1+ EVs have various cell origins, so further analysis of the subpopulations is essential to help understand better their relationship with tumor immunotherapy. Different from the previous work which focus on the level of total PD-L1+ EVs expression, we, herein, report a dual-recognition mediated autocatalytic amplification (DRMAA) assay to detect the PD-L1 derived from tumors (EpCAM+), immune T cells (CD3+), and total (Lipids) EVs, respectively. The DRMAA assay employed proximity hybridization to construct a complete trigger sequence and then catalyzed the cross-hybridization of three hairpin probes, producing a three-way DNA junction (3-WJ) structure carrying the newly exposed trigger sequence. The 3-WJ complex subsequently initiated an autocatalytic amplification reaction and higher sensitivity than the traditional catalytic hairpin assembly assay was obtained. It was found that the EpCAM+ and PD-L1+ EVs were more effective than others in distinguishing lung cancer patients from healthy people. Surprisingly, the CD3+ and PD-L1+ EVs in lung cancer patients were also upregulated, indicating that immune cell-derived PD-L1+ EVs are also non-negligible marker in a tumor microenvironment. Our results suggested that the DRMAA assay would improve the study of subpopulations of PD-L1+ EVs to provide new insights for cancer immunotherapies.


Asunto(s)
Antígeno B7-H1 , Vesículas Extracelulares , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Catálisis , Molécula de Adhesión Celular Epitelial/metabolismo , Técnicas de Amplificación de Ácido Nucleico , Biomarcadores de Tumor , Hibridación de Ácido Nucleico
5.
Small ; : e2403600, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949410

RESUMEN

BiVO4-based photoanode is one of the most promising photoanodes for photoelectrocatalytic water splitting. However, the serious problem of interface charge recombination limits its further development. Here, a Mo:BiVO4/NiOx/CPF-TCzB/NiCoBi photoanode is constructed with double hole transport layer and an energy level gradient to achieve an effective photo-generated holes extraction and accumulation at the surface electrocatalyst. The conjugated polycarbazole framework CPF-TCzB is used as hole transport layer to eliminate the charge recombination center between Mo:BiVO4 and NiCoBi electrocatalyst and realize the extraction and storage of photo-generated hole; NiOx nanoparticles are further inserted between Mo:BiVO4 and CPF-TCzB to form a gradient energy level, eliminating the energy level barrier and optimizing band alignment. As a result, Mo:BiVO4/NiOx/CPF-TCzB/NiCoBi achieves a much higher photocurrent densities of 3.14 mA cm-2 than that of Mo:BiVO4 (0.42 mA cm-2) at 0.6 V versus RHE. This work provides an specific way to adjust the band structure of BiVO4-based photoanodes and realize efficient hole extraction and storage for PEC water splitting.

6.
Chemphyschem ; 25(15): e202400053, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38706399

RESUMEN

The study of fluid absorption, particularly that of water, into nanoporous materials has garnered increasing attention in the last decades across a broad range of disciplines. However, most investigation approaches to probe such behaviors are limited by characterization conditions and may lead to misinterpretations. In this study, a combined MRI and MAS NMR method was used to study a nanoporous silica glass to acquire information about its structural framework and interactions with confined water in a native humid environment. Specifically, MRI was used for a quantitative analysis of water extent. While MAS NMR techniques provided structural information of silicate materials, including interactive surface area and framework packing. Analysis of water spin-spin relaxation times (T2) suggested differences in water confinement within the characterized framework. Subsequent unsuccessful delivery of paramagnetic molecule into the pores enabled a quantitative assessment of the dimensions that "bottleneck" the pores. Finally, pore sizes were derived from the paramagnetic molecular size, density function theory (DFT) simulation and characterizations on standard samples. Our result matches with Brunauer-Emmett-Teller (BET) analysis that the pore size is less than 1.3 nm. The use of a paramagnetic probe for pore size determination introduces a new approach of characterization in the liquid phase, offering an alternative to the conventional BET analysis that uses gas molecule as probes.

7.
Acta Pharmacol Sin ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38942954

RESUMEN

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

8.
Arch Orthop Trauma Surg ; 144(3): 1269-1279, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38195950

RESUMEN

INTRODUCTION: To date, the approach that prevails in the open reduction and internal fixation of crescent fracture-dislocations (CFD) remains unknown. This study aimed to compare the outcomes of CFD treated via the anterior or posterior approach. MATERIALS AND METHODS: Data from 64 cases of CFDs openly reduced through an anterior (group A, n = 31) or a posterior (group B, n = 33) approach were retrospectively analyzed. Functional results, reduction quality, residual displacements in the axial and coronal planes, pelvic asymmetry deformity, and correlations between Day's classification were compared. Complications and fracture union were also recorded. All patients were followed up for at least 12 months. RESULTS: The functional scores were similar between the two groups, and all fractures achieved good or excellent reduction postoperatively. In the coronal plane, the excellent/good ratio in group B was higher than in group A. The mean residual displacement in the coronal plane was significantly higher in group A than in group B, with group A showing greater displacement in both planes for Day I fractures and in the coronal plane for Day II fractures. The residual displacement in both planes for Day III fractures was comparable between the groups. The pelvic asymmetry deformity was equal between the two groups and among the different Day's fracture types. CONCLUSIONS: Open reduction and internal fixation of CFDs obtained satisfactory outcomes through an anterior or posterior approach. The posterior approach achieved a better sacroiliac joint reduction. The optimal indication for the posterior approach was a Day I fracture, followed by a Day II fracture. No correlation was found between the surgical approach and reduction quality in Day III fractures.


Asunto(s)
Fractura-Luxación , Fracturas Óseas , Humanos , Estudios Retrospectivos , Tornillos Óseos , Fracturas Óseas/cirugía , Fijación Interna de Fracturas/métodos , Reducción Abierta , Fractura-Luxación/cirugía , Resultado del Tratamiento
9.
World J Gastrointest Oncol ; 16(8): 3738-3740, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39171168

RESUMEN

A study on clinical outcomes and prognostic factors in T4N0M0 colon cancer patients after R0 resection revealed that ileostomy, T stage, right hemicolectomy, irregular follow-up, and CA199 level were independent risk factors affecting overall survival. T4-stage cancer invades the entire thickness of the intestinal tract, increasing the difficulty of treatment and the risk of recurrence, and requires a combination of chemotherapy, immunotherapy, and targeted therapy to control the spread of cancer cells. The prognosis of right hemicolectomy is significantly worse than that of left hemicolectomy, and right hemicolectomy is an independent risk factor for a poor prognosis. Advanced age, histopathological type, and lymph node metastasis are also risk factors for colon cancer.

10.
Updates Surg ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38568357

RESUMEN

PURPOSE: To compare the surgical safety and postoperative quality of life (QOL) between side overlap anastomosis (SOA) and double-tract anastomosis (DTA) after laparoscopic proximal gastrectomy (LPG). METHODS: This retrospective cohort study included 43 patients with proximal gastric cancer (PGC) who underwent LPG and were admitted to the Second Affiliated Hospital of Fujian Medical University between August 2020 and December 2022 were in. Their clinical and follow-up data were collected. The patients were divided into the modified SOA (mSOA) (n = 20) and DTA (n = 23) groups based on the anastomosis methods used. The main outcome measures included the QOL of patients 1 year after surgery, and the evaluation criteria were based on the postgastrectomy syndrome assessment scale. Secondary outcome measures included intraoperative and postoperative conditions, postoperative long-term complications and nutritional status 3, 6 and 12 months after surgery. RESULTS: No significant differences were observed in intraoperative and postoperative conditions (P > 0.05) between the mSOA and DTA groups. The mSOA group showed a decreased incidence of reflux esophagitis 1 year after surgery compared with the DTA group (P < 0.05), and no statistically significant differences were noticed between the two groups in terms of other postoperative complications (P > 0.05). The mSOA group showed better QOL when compared with the DTA group (P < 0.05). No significant differences were recorded in postoperative nutritional status between the two groups (P > 0.05). CONCLUSION: The efficacy and safety of LPG with mSOA for PGC were comparable. When compared with the DTA group, the mSOA group seems to show reduced incidence of gastroesophageal reflux and improved QOL, which makes mSOA one of the ideal surgical methods for PGC.

11.
PLoS One ; 19(7): e0307077, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39008436

RESUMEN

BACKGROUND: LLNM can occur in mid-low rectal cancer, but LLND in patients with rectal cancer presents certain challenges. Recent years have seen the progressive application of ICG fluorescence imaging technology in colorectal surgery. This study aimed to explore the effectiveness of ICG-guided laparoscopic LLND for rectal cancer. METHODS: We applied ICG-guided laparoscopic lateral lymph node dissection in 11 patients diagnosed as rectal cancer with lateral lymph node metastasis. RESULTS: All 11 patients in this group successfully completed ICG-guided laparoscopic LLND for rectal cancer with good lateral lymph node imaging. CONCLUSIONS: ICG-guided laparoscopic LLND for rectal cancer is safe and represents a feasible solution, thereby providing valuable guidance for intraoperative lymph node dissection.


Asunto(s)
Verde de Indocianina , Laparoscopía , Escisión del Ganglio Linfático , Neoplasias del Recto , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/diagnóstico por imagen , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Metástasis Linfática , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/diagnóstico por imagen
12.
World J Gastrointest Surg ; 16(1): 113-123, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38328314

RESUMEN

BACKGROUND: With the increasing incidence of proximal gastric cancer, laparoscopic proximal gastrectomy has been applied. However, reflux esophagitis often occurs after traditional esophagogastric anastomosis. In order to solve this problem, several methods of digestive tract reconstruction have emerged, but the most satisfying method remains to be discussed. Therefore, we modified traditional Kamikawa anastomosis to investigate the appropriate digestive tract reconstruction in laparoscopic proximal gastrectomy. AIM: To discuss the clinical efficacy of modified Kamikawa anastomosis in laparoscopic proximal gastrectomy. METHODS: A retrospective case series was adopted. Clinicopathological data were collected from 26 patients who underwent laparoscopic proximal gastrectomy and modified Kamikawa anastomosis at our hospital from January 2020 to September 2022. The operation conditions, postoperative recovery, postoperative complications, and follow-up data were collected and analyzed. RESULTS: All the patients were successfully operated on without conversion to laparotomy. The duration of operation and digestive tract reconstruction were 203.500 (150-224) min and 87.500 (73-111) min, respectively. The intraoperative amount of bleeding was 20.500 mL ± 0.696 mL. The time of postoperative first flatus, the first postoperative fluid intake, and the postoperative length of stay were 2 (1-3) d, 4 (3-5) d, and 9 (8-10) d, respectively. All the patients were followed up for 12-23 months. The body mass index at 6 and 12 months after surgery were 22.577 kg/m2 ± 3.098 kg/m2 and 22.594 kg/m2 ± 3.207 kg/m2, respectively. The nutrition risk screening 2002 score, the patient-generated subjective global assessment score, and the gastroesophageal reflux disease scale score were good at 6 and 12 months after surgery. Reflux esophagitis and anastomotic stenosis were not observed in any of the patients during their 12-month postoperative gastroscopy or upper gastrointestinal tract visits. All the patients exhibited no tumor recurrence or metastasis. CONCLUSION: The modified Kamikawa anastomosis is safe and feasible for laparoscopic proximal gastrectomy and has good antireflux effects and nutritional status.

13.
Sci Rep ; 14(1): 17181, 2024 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060330

RESUMEN

To investigate the short-term clinical efficacy of laparoscopic proximal gastrectomy with modified Kamikawa anastomosis and laparoscopic total gastrectomy with Roux-en-Y anastomosis. Retrospective cohort study was conducted. The clinicopathological data of 268 patients who underwent laparoscopic proximal gastrectomy for adenocarcinoma of esophagogastric junction and upper gastric adenocarcinoma from January 2016 to October 2022 were collected. Among 268 patients, 26 underwent laparoscopic proximal gastrectomy with modified Kamikawa anastomosis were assigned to Kamikawa group and 242 underwent laparoscopic total gastrectomy with Roux-en-Y anastomosis were assigned to Roux-en-Y group. The sex, age, BMI, preoperative albumin, maximum tumor diameter, histological grade, and pathological stage of patients in the Kamikawa group and the Roux-en-Y group were subjected to 1:1 propensity score matching. After matching, 16 patients in Kamikawa group and Roux-en-Y group were respectively included in this study. Outcome measures: (1) Intraoperative condition. (2) Postoperative recovery. (3) Follow-up information. The patients' nutritional status, reflux esophagitis and anastomotic stoma were investigated by outpatient and telephone follow-up. Nutritional status assessment comprising body mass index and Nutritional Risk Screening 2002 score. (1) Intraoperative condition. All patients successfully underwent laparoscopic proximal gastrectomy and total gastrectomy. Compared with Roux-en-Y group, the digestive tract reconstruction time in Kamikawa group was longer 93.0(74.0-111.0)min vs. 39.7(35.1-46.2)min, t = -2.001, P = 0.055., and the difference was statistically significant (P < 0.05). There was no statistically significant difference in total operation time and intraoperative blood loss (P > 0.05). (2) Postoperative recovery. There was no statistically significant difference between Kamikawa group and Roux-en-Y group in first anal exhaust time, first postoperative liquid intake time, postoperative hospitalization time, and postoperative complications (P > 0.05). (3) Follow-up information. All patients were followed up. BMI and NRS 2002 scores in Kamikawa group were better than those in Roux-en-Y group at 6 and 12 months after surgery 22.9 ± 3.0 kg/m2 vs. 20.8 ± 2.2 kg/m2, t = 2.165, P = 0.038; 23.1 ± 3.0 kg/m2 vs. 20.3 ± 2.2 kg/m2, t = 3.022, P = 0.005 and 2 (1-2) vs. 2 (1-3), Z = -2.585, P = 0.010; 2 (1-2) vs. 2 (1-3), Z = -2.273, P = 0.023., the difference was statistically significant (P < 0.05). There was no significant difference in GERD scale score and occurrence of ≥ Grade B reflux esophagitis at 6 and 12 months after surgery between Kamikawa group and Roux-en-Y group (P > 0.05). Anastomotic stenosis was not found in all patients by postoperative upper gastrointestinal angiography. Laparoscopic proximal gastrectomy with modified Kamikawa anastomosis is safe and feasible for the treatment of esophagogastric junction and upper gastric adenocarcinoma, and can achieve good anti-reflux effect. Besides, compared with traditional laparoscopic total gastrectomy, its postoperative nutritional status is better.


Asunto(s)
Anastomosis en-Y de Roux , Gastrectomía , Laparoscopía , Neoplasias Gástricas , Humanos , Masculino , Gastrectomía/métodos , Femenino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Persona de Mediana Edad , Anastomosis en-Y de Roux/métodos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Anastomosis Quirúrgica/métodos , Anastomosis Quirúrgica/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Unión Esofagogástrica/cirugía , Unión Esofagogástrica/patología
14.
Updates Surg ; 76(2): 513-520, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38245891

RESUMEN

According to past and current literature, metastasis of the lymph nodes at the inferior mesenteric artery (IMA-LN), also known as 253LN of colorectal cancer has been seldom investigated. To date, there are still controversies on whether the 253LN need to be routinely cleaned. Using specific criteria, 347 patients who underwent radical resection for rectal cancer between April 2019 and July 2022 were selected for the study. Logistic regression was used to determine the likelihood that a patient may suffer 253LN metastasis, and a nomogram for 253LN metastasis subsequently developed. The c-index and calibration curve were used to evaluate precision and discrimination in the nomogram, and the appropriateness of the final nomogram for the clinical setting determined using decision curve analysis (DCA). 253LN metastases appeared in the pathological specimens of 29 (8.4%) of the selected patients. Logistic regression showed that preoperative parameters including serum carcinoembryonic antigen (CEA) value ( > 5 ng / ml, OR = 2.894, P = 0.023), distance from anal margin (> 9 cm, OR = 2.406, P = 0.045) and degree of differentiation (poor, OR = 9.712, P < 0.001) were significantly associated with 253LN metastasis. A nomogram to predict 253LN metastasis in rectal cancer was developed and showed considerable discrimination and good precision (c-index = 0.750). Furthermore, DCA confirmed that the nomogram has some feasibility for the clinical environment. Clinicopathological and radiological patient data can be pivotal for making surgical decisions relating to 253LN metastasis. A nomogram was developed using this data, providing an objective method that can significantly improve prognoses in colorectal cancer.


Asunto(s)
Nomogramas , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Estudios de Casos y Controles , Arteria Mesentérica Inferior/cirugía , Arteria Mesentérica Inferior/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Ganglios Linfáticos/patología , Metástasis Linfática/patología
15.
Artículo en Inglés | MEDLINE | ID: mdl-38862430

RESUMEN

Tandem duplication (TD) is a major type of structural variations (SVs) that plays an important role in novel gene formation and human diseases. However, TDs are often missed or incorrectly classified as insertions by most modern SV detection methods due to the lack of specialized operation on TD-related mutational signals. Herein, we developed a TD detection module for the Pindel tool, referred to as Pindel-TD, based on a TD-specific pattern growth approach. Pindel-TD is capable of detecting TDs with a wide size range at single nucleotide resolution. Using simulated and real read data from HG002, we demonstrated that Pindel-TD outperforms other leading methods in terms of precision, recall, F1-score, and robustness. Furthermore, by applying Pindel-TD to data generated from the K562 cancer cell line, we identified a TD located at the seventh exon of SAGE1, providing an explanation for its high expression. Pindel-TD is available for non-commercial use at https://github.com/xjtu-omics/pindel.


Asunto(s)
Programas Informáticos , Humanos , Células K562 , Duplicación de Gen , Secuencias Repetidas en Tándem/genética , Algoritmos
16.
ACS Biomater Sci Eng ; 10(5): 3136-3147, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38663028

RESUMEN

Treatment with immune checkpoint inhibitors (ICIs) has shown efficacy in some patients with Lynch syndrome-associated colon cancer, but some patients still do not benefit from it. In this study, we adopted a combination strategy of tumor vaccines and ICIs to maximize the benefits of immunotherapy. Here, we obtained tumor-antigen-containing cell lysate (TCL) by lysing MC38Mlh1 KD cells and prepared liposome nanoparticles (Lipo-PEG) with a typical spherical morphology by thin-film hydration. Anti-PD-L1 was coupled to the liposome surface by the amidation reaction. As observed, anti-PD-L1/TCL@Lipo-PEG was not significantly toxic to mouse intestinal epithelial cells (MODE-K) in the safe concentration range and did not cause hemolysis of mouse red blood cells. In addition, anti-PD-L1/TCL@Lipo-PEG reduced immune escape from colon cancer cells (MC38Mlh1 KD) by the anti-PD-L1 antibody, restored the killing function of CD8+ T cells, and targeted more tumor antigens to bone marrow-derived dendritic cells (BMDCs), which also expressed PD-L1, to stimulate BMDC antigen presentation. In syngeneic transplanted Lynch syndrome-associated colon cancer mice, the combination of anti-PD-L1 and TCL provided better cancer suppression than monoimmunotherapy, and the cancer suppression effect of anti-PD-L1/TCL@Lipo-PEG treatment was even better than that of the free drug. Meanwhile anti-PD-L1/TCL@Lipo-PEG enhanced the immunosuppressive tumor microenvironment. In vivo fluorescence imaging and H&E staining showed that the nanomedicine was mainly retained in the tumor site and had no significant toxic side effects on other major organs. The anti-PD-L1/TCL@Lipo-PEG prepared in this study has high efficacy and good biosafety in alleviating the progression of Lynch syndrome-associated colon cancer, and it is expected to be a therapeutic candidate for Lynch syndrome-associated colon cancer.


Asunto(s)
Antígeno B7-H1 , Neoplasias del Colon , Neoplasias Colorrectales Hereditarias sin Poliposis , Liposomas , Animales , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Neoplasias del Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Ratones , Antígeno B7-H1/metabolismo , Nanomedicina , Línea Celular Tumoral , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Humanos , Ratones Endogámicos C57BL , Femenino , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Nanopartículas/química , Nanopartículas/uso terapéutico , Progresión de la Enfermedad , Polietilenglicoles/química , Polietilenglicoles/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígenos de Neoplasias/inmunología
17.
Huan Jing Ke Xue ; 45(1): 335-342, 2024 Jan 08.
Artículo en Zh | MEDLINE | ID: mdl-38216483

RESUMEN

The composition of soil organic carbon and its stability mechanism are the key to understanding the terrestrial carbon sink capacity. The stability of soil organic carbon in a karst ecosystem greatly affects the soil carbon fixation capacity. In order to understand the impact of human activities on the stability of soil organic carbon in karst areas, the karst valley area of Zhongliang Mountain in Chongqing was selected as an example, and soil samples of four typical land use modes (mixed forest, bamboo forest, grassland, and cultivated land) were collected in layers to analyze the total organic carbon (TOC) and heavy fraction organic carbon (HFOC). The distribution characteristics of light fraction organic carbon (LFOC), labile organic carbon (LOC), and recalcitrant organic carbon (ROC) were analyzed quantitatively by using a structural equation model to provide basic data for soil carbon sink assessment and soil quality protection in karst areas. The results showed that the organic carbon components under different land use patterns in karst areas had obvious surface accumulation, and the content of organic carbon components in the surface layer was 1.2 times that in the bottom layer. Except for LFOC, the content of other organic carbon components was the highest in the mixed forest, followed by that in the bamboo forest and wasteland, with the lowest in cultivated land. Mixed forest ω(TOC) content was the highest, 42.5 g·kg-1, followed by that of bamboo forest (36.6 g·kg-1) and grassland (18.7 g·kg-1), and cultivated land content was the lowest, 13.4 g·kg-1. The soil organic carbon content of cultivated land was 68.5%, 63.5%, and 28.3% lower than that of mixed forest, bamboo forest, and grassland, respectively. Mixed forest had the highest content of ω(HFOC), 21 g·kg-1, followed by those of bamboo forest (20.9 g·kg-1), grassland (18.2 g·kg-1), and cultivated land (13.5 g·kg-1). The mixed forest ω(LOC) content was the highest, 16.3 g·kg-1, followed by those of bamboo forest (14.9 g·kg-1), grassland (11.5 g·kg-1), and cultivated land (5.3 g·kg-1). Mixed forest ω (ROC) content was the highest, 25.7 g·kg-1, followed by those of bamboo forest (21.6 g·kg-1), grassland (15.9 g·kg-1), and cultivated land (10.3 g·kg-1). The bamboo forest land ω(LFOC) content was 15.9 g·kg-1, followed by those of mixed forest (13.9 g·kg-1), grassland (7.3 g·kg-1), and cultivated land (4.9 g·kg-1). The recalcitrant organic carbon index (ROCI) was used to indicate the stability of soil organic carbon. The variation range of ROCI was 33.9%-64.5%, of which the highest was mixed forest (64.5%-66.3%), and the lowest was cultivated land (33.8%-39.6%). The ROCI of mixed forest, bamboo forest, and grassland were 1.8 times, 1.6 times, and 1.4 times that of cultivated land, respectively. Karst area ω (inert organic carbon) content and ROCI showed that human agricultural activities caused the reduction in soil organic carbon content and the destruction of soil physical structure, resulting in the accelerated decomposition and turnover rate of soil organic matter. The most important factor affecting soil stability in karst areas was soil pH. Tillage activities caused soil pH to rise, reduced soil microbial activity, and were not conducive to the accumulation of the inert organic carbon and soil organic carbon pool in the soil.

18.
ACS Appl Mater Interfaces ; 16(20): 26217-26225, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38733352

RESUMEN

Among various anode materials, SiOx is regarded as the next generation of promising anode due to its advantages of high theoretical capacity with 2680 mA h g-1, low lithium voltage platform, and rich natural resources. However, the pure SiOx-based materials have slow lithium storage kinetics attributed to their low electron/ion conductive properties and the large volume change during lithiation/delithiation, restricting their practical application. Optimizing the SiOx material structures and the fabricating methods to mitigate these fatal defects and adapt to the market demand for energy density is critical. Hence, SiOx material with TiO1-xNx phase modification has been prepared by simple, low-cost, and scalable ball milling and then combined with nitridation. Consequently, based on the TiO1-xNx modified layer, which boosts high ionic/electronic conductivity, chemical stability, and excellent mechanical properties, the SiOx@TON-10 electrode shows highly stable lithium-ion storage performance for lithium-ion half/full batteries due to a stable solid-electrolyte interface layer, fast Li+ transport channel, and alleviative volumetric expansion, further verifying its practical feasibility and universal applicability.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38862426

RESUMEN

The high-fidelity (HiFi) long-read sequencing technology developed by PacBio has greatly improved the base-level accuracy of genome assemblies. However, these assemblies still contain base-level errors, particularly within the error-prone regions of HiFi long reads. Existing genome polishing tools usually introduce overcorrections and haplotype switch errors when correcting errors in genomes assembled from HiFi long reads. Here, we describe an upgraded genome polishing tool - NextPolish2, which can fix base errors remaining in those "highly accurate" genomes assembled from HiFi long reads without introducing excessive overcorrections and haplotype switch errors. We believe that NextPolish2 has a great significance to further improve the accuracy of telomere-to-telomere (T2T) genomes. NextPolish2 is freely available at https://github.com/Nextomics/NextPolish2.


Asunto(s)
Programas Informáticos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Humanos , Genómica/métodos , Secuencias Repetitivas de Ácidos Nucleicos/genética , Genoma/genética
20.
Adv Healthc Mater ; 13(19): e2304648, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38597827

RESUMEN

Drug-resistant and metastatic cancer cells such as a small population of cancer stem cells (CSCs) play a crucial role in metastasis and relapse. Conventional small-molecule chemotherapeutics, however, are unable to eradicate drug-resistant CSCs owing to limited interface inhibitory effects. Herein, it is reported that enhanced interfacial inhibition leading to eradication of drug-resistant CSCs can be dramatically induced by self-insertion of bioactive graphene quantum dots (GQDs) into DNA major groove (MAG) sites in cancer cells. Since transcription factors regulate gene expression at the MAG site, MAG-targeted GQDs exert greatly enhanced interfacial inhibition, downregulating the expression of a collection of cancer stem genes such as ALDH1, Notch1, and Bmi1. Moreover, the nanoscale interface inhibition mechanism reverses cancer multidrug resistance (MDR) by inhibiting MDR1 gene expression when GQDs are used at a nontoxic concentration (1/4 × half-maximal inhibitory concentration (IC50)) as the MDR reverser. Given their high efficacy in interfacial inhibition, CSC-mediated migration, invasion, and metastasis of cancer cells can be substantially blocked by MAG-targeted GQDs, which can also be harnessed to sensitize clinical cytotoxic agents for improved efficacy in combination chemotherapy. These findings elucidate the inhibitory effects of the enhanced nano-bio interface at the MAG site on eradicating CSCs, thus preventing cancer metastasis and recurrence.


Asunto(s)
Resistencia a Antineoplásicos , Grafito , Células Madre Neoplásicas , Puntos Cuánticos , Humanos , Grafito/química , Grafito/farmacología , Puntos Cuánticos/química , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Familia de Aldehído Deshidrogenasa 1/metabolismo , Movimiento Celular/efectos de los fármacos , Retinal-Deshidrogenasa/metabolismo , Metástasis de la Neoplasia , Receptor Notch1/metabolismo , Receptor Notch1/genética , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/antagonistas & inhibidores , Antineoplásicos/farmacología , Antineoplásicos/química , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Animales
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