CD169 Expression in Lymph Nodes is Associated with Increased Infiltration of CD8+ T Cells in Tumors: A Systematic Review and Meta-Analysis.

The density of CD169+ macrophages has been reported to positively correlate with the number of CD8+ T cells, although this remains controversial. To better understand this topic, we conducted a meta-analysis. We searched the PubMed, Medline, and Web of Science databases for studies that were published before May 2022 and performed a meta-analysis of the incidence of low and high CD169 expression in groups based on CD8 expression using the random-effects model. A total of 10 studies were included in the meta-analysis. The incidence of high CD169 expression in lymph nodes was significantly lower than that of low CD169 expression in the low CD8 expression group (odds ratio (OR): 0.76, 95% confidence interval (CI): 0.6, 0.96); however, the incidence of high CD169 expression in lymph nodes was higher than that of low CD169 expression in the high CD8 expression group (OR: 1.50, 95% CI: 1.08, 2.07). We also found that the expression of CD169 in tumors was lower than that in nontumor tissues (standardized mean difference: -5.29, 95% CI: -7.47, -3.11). The overall survival and hazard ratio of patients with high and low CD169 expression was 0.45 (95% CI: 0.37, 0.55). This analysis showed that high CD169 expression was associated with a high CD8 expression, and low CD169 expression was associated with low CD8 expression. The risk of death was 55% lower for patients with high CD169 expression, and high CD169 expression may be associated with favorable survival outcomes in cancer patients. However, the number and heterogeneity of the studies should be taken into consideration when evaluating the analysis. High-quality randomized controlled trials on the association between CD169 and CD8 expression are needed to verify these effects.

Yiqi Yangjing recipe stimulates apoptosis while suppressing the energy metabolism via under-expression of PFKFB3 in A549 cells.

Background: Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer. Methods: The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3-under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR. Results: YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues. Conclusions: This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3. Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment.

Inosine enhances tumor mitochondrial respiration by inducing Rag GTPases and nascent protein synthesis under nutrient starvation.

Metabolic heterogeneity of tumor microenvironment (TME) is a hallmark of cancer and a big barrier to cancer treatment. Cancer cells display diverse capacities to utilize alternative carbon sources, including nucleotides, under poor nutrient circumstances. However, whether and how purine, especially inosine, regulates mitochondrial metabolism to buffer nutrient starvation has not been well-defined yet. Here, we identify the induction of 5'-nucleotidase, cytosolic II (NT5C2) gene expression promotes inosine accumulation and maintains cancer cell survival in the nutrient-poor region. Inosine elevation further induces Rag GTPases abundance and mTORC1 signaling pathway by enhancing transcription factor SP1 level in the starved tumor. Besides, inosine supplementary stimulates the synthesis of nascent TCA cycle enzymes, including citrate synthesis (CS) and aconitase 1 (ACO1), to further enhance oxidative phosphorylation of breast cancer cells under glucose starvation, leading to the accumulation of iso-citric acid. Inhibition of the CS activity or knockdown of ACO1 blocks the rescue effect of inosine on cancer survival under starvation. Collectively, our finding highlights the vital signal role of inosine linking mitochondrial respiration and buffering starvation, beyond serving as direct energy carriers or building blocks for genetic code in TME, shedding light on future cancer treatment by targeting inosine metabolism.

Calorie restriction remodels gut microbiota and suppresses tumorigenesis of colorectal cancer in mice.

Colorectal cancer (CRC) is one of the most common cancers worldwide and the consumption of a high-calorie diet is one of its risk factors. Calorie restriction (CR) slows tumor growth in a variety of cancers, including colorectal cancer; however, the mechanism behind this remains unknown. In the present study, CR effectively reduced the tumor volume and weight in a xenograft BALB/c male nude mouse model. In addition, tumor immunohistochemistry revealed that the CR group had significantly higher expression of Bax (P<0.001) and significantly lower levels of Bcl2 (P<0.0001) and Ki67 (P<0.001) compared with control group. Furthermore, data from 16S ribosomal (r)RNA sequencing implied that CR was able to reprogram the microbiota structure, characterized by increased Lactobacillus constituent ratio (P<0.05), with amelioration of microbial dysbiosis caused by CRC. Further receiver operating characteristic curves demonstrated that the bacteria Bacteroides [area under the curve (AUC)=0.800], Lactobacillus (AUC=0.760) and Roseburia (AUC=0.720) served key roles in suppression of CRC in the mouse model. The functional prediction of intestinal flora indicated 'cyanoamino acid metabolism' (P<0.01), 'replication initiation protein REP (rolling circle plasmid replication)' (P<0.01), 'tRNA G10 N-methylase Trm11' (P<0.01) and 'uncharacterized protein with cyclophilin fold, contains DUF369 domain' (P<0.05) were downregulated in CR group. These findings implied that CR suppressed CRC in mice and altered the gut microbiota.

Effect of laparoscopic surgery for colorectal cancer with N. O. S. E. on recovery and prognosis of patients.

OBJECTIVE: To investigate the effect of laparoscopic surgery in colorectal cancer (CRC) patients with natural orifice specimen extraction (NOSE) on the recovery and quality of life (QOL) of patients. MATERIAL AND METHODS: Ninety-two eligible patients were randomly assigned into two groups: the traditional laparoscopy group (L group, n = 46) and the laparoscopic transanal specimen extraction group (NL group, n = 46). General data, surgery-related indicators, postoperative recovery, and prognosis were compared and analyzed between the two groups. RESULTS: A total of 46 patients in each group were enrolled in this study. The general data and surgery-related indicators were comparable between the two groups (all p > .05). There were no significant differences in the time of first flatus, bleeding, obstruction, constipation, and infectious complications between the two groups (all p > .05). The differences in the incidence of postoperative diarrhea, pain degree, and satisfaction on the aesthetics of the abdominal wall showed significant differences (χ2 = 6.133, p = .013; χ2 = 12.116, p = .017; χ2 = 13.463, p = .004). The postoperative follow-up time was 3-53 months. There were no significant differences in the postoperative hospital stay, medical costs, hospital readmission rate, incidence of incisional hernia, overall survival, disease-free survival, and QOL between the two groups (all p > .05). Conclusion: Laparoscopic surgery with NOSE for eligible patients with CRC was a feasible choice.

Comprehensive analysis of plasmid-mediated tet(X4)-positive Escherichia coli isolates from clinical settings revealed a high correlation with animals and environments-derived strains.

The emergence of novel plasmid-mediated high-level tigecycline resistance genes tet(X) in the Enterobacteriaceae has increased public health risk for treating severe bacterial infections. Despite growing reports of tet(X)-positive isolates detected in animal sources, the epidemiological association of animal- and environment-derived isolates with human-derived isolates remains unclear. Here, we performed a comprehensive analysis of tet(X4)-positive Escherichia coli isolates collected in a hospital in Guangdong province, China. A total of 48 tet(X4)-positive E. coli isolates were obtained from 1001 fecal samples. The tet(X4)-positive E. coli isolates were genetically diverse but certain strains that belonged to ST48, ST10, and ST877 etc. also have clonally transmitted. Most of the tet(X4) genes from these patient isolates were located on conjugative plasmids that were successfully transferred (64.6%) and generally coexisted with other antibiotic resistance genes including aadA, floR, blaTEM and qnrS. More importantly, we found the IncX1 type plasmid was a common vector for tet(X4) and was prevalent in these patient-derived strains (31.3%). This plasmid type has been detected in animal-derived strains from different species in different regions demonstrating its strong transmission ability and wide host range. Furthermore, phylogenetic analysis revealed that certain strains of patient and animal origin were closely related indicating that the tet(X4)-positive E. coli isolates were likely to have cross-sectorial clonal transmission between humans, animals, and farm environments. Our research greatly expands the limited epidemiological knowledge of tet(X4)-positive strains in clinical settings and provides definitive evidence for the epidemiological link between human-derived tet(X4)-positive isolates and animal-derived isolates.

Zhengyuan capsule for the treatment of cancer-related fatigue in lung cancer patients undergoing operation: a study protocol for a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Zhengyuan capsule () when treating Cancer-related fatigue (CRF) in lung cancer patients undergoing surgical operation. METHODS/DESIGN: This is a single-center, double-blinded, prospective, and randomized controlled trial in the Department of Integrated Chinese and Western Medicine, Shanghai Chest Hospital Shanghai JiaoTong University, Shanghai. Eligible participants will be randomly allocated into two groups: a treatment group receiving an 8-week Zhengyuan capsule regimen therapy and a control group receiving an 8-week placebo capsule regimen therapy. Evaluation will be carried out at four timelines: the participants' screening period, baseline period, the middle of the intervention period, and the end of the intervention period. The primary outcome assessment is fatigue scoring using the Cancer Fatigue Scale (CFS) measurement system. Secondary measurements include fatigue severity assessment using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) measurement system, Traditional Chinese Medicine syndrome pattern differentiation, levels of immunologic indicators (TNF-α, IL-6, IL-1, T lymphocytes subsets and B lymphocyte subsets), patient's pulmonary function, performance status scale (PS), self-rating scale of sleep (SRSS), and adverse events (AEs). DISCUSSION: The trial results can provide efficacy and safety data of Zhengyuan capsule when treating CRF in clinic. The data can also be imported into the management and treatment guidelines for CRF in lung cancer patients undergoing operation throughout China.

Role of Removed Lymph Nodes on the Prognosis of M0 Small-Bowel Neuroendocrine Tumors: a Propensity Score Matching Analysis from SEER Database.

BACKGROUND: Current studies on the number of removed lymph nodes (LNs) and their prognostic value in small-bowel neuroendocrine tumors (SBNETs) are limited. This study aimed to clarify the prognostic value of removed LNs for SBNETs. METHODS: SBNET patients without distant metastasis from 2004 to 2017 in the SEER database were included. The optimal cutoff values of examined LNs (ELNs) and negative LNs (NLNs) were calculated by the X-tile software. Propensity score matching (PSM) was done to match patients 1:1 on clinicopathological characteristics between the two groups. The Kaplan-Meier method with log-rank test and multivariable Cox proportional-hazards regression model were used to evaluate the prognostic effect of removed LNs. RESULTS: The cutoff values of 14 for ELNs and 9 for NLNs could well distinguish patients with different prognoses. After 1:1 PSM, the differences in clinicopathological characteristics between the two groups were significantly reduced (all P > 0.05). Removal of more than one LN significantly improved the prognosis of the patients (P < 0.001). The number of lymphatic metastasis in the sufficiently radical resection group (SRR, 3.74 ± 3.278, ELN > 14 and NLN > 9) was significantly more than that in the insufficiently radical resection group (ISRR, 2.72 ± 3.19, ELN < 14 or NLN < 9). The 10-year overall survival (OS) of the SRR was significantly better than that of the ISRR (HR = 1.65, P = 0.001, 95% CI: 1.24-2.19). CONCLUSION: Both ELNs and NLNs can well predict the OS of patients. Systematic removal of more than 14 LNs and more than 9 NLNs can increase the OS of SBNET patients.

Critical prognostic value of the log odds of negative lymph nodes/tumor size in rectal cancer patients.

BACKGROUND: The number of negative lymph nodes (NLNs) and tumor size are associated with prognosis in rectal cancer patients undergoing surgical resection. However, little is known about the prognostic significance of the NLN count after adjusting for tumor size. AIM: To assess the prognostic impact of the log odds of NLN/tumor size (LONS) in rectal cancer patients. METHODS: Data of patients with stage I-III rectal cancer were extracted from the Surveillance, Epidemiology, and End Results Program database. These patients were randomly divided into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of the LONS. The optimal cutoff values of LONS were calculated using the "X-tile" program. Stratified analysis of the effect of LONS on cancer-specific survival (CSS) and overall survival (OS) were performed. The Kaplan-Meier method with the log-rank test was used to plot the survival curve and compare the survival data among the different groups. RESULTS: In all, 41080 patients who met the inclusion criteria were randomly divided into a training cohort (n = 28775, 70%) and a validation cohort (n = 12325, 30%). Univariate and multivariate analyses identified the continuous variable LONS as an independent prognostic factor for CSS [training cohort: Hazard ratio (HR) = 0.47, 95% confidence interval (CI): 0.44-0.51, P < 0.001; validation cohort: HR = 0.46, 95%CI: 0.41-0.52, P < 0.001] and OS (training cohort: HR = 0.53, 95%CI: 0.49-0.56, P < 0.001; validation cohort: HR = 0.52, 95%CI: 0.42-0.52, P < 0.001). The X-tile program indicated that the difference in CSS was the most significant for LONS of -0.8, and the cutoff value of -0.4 can further distinguish patients with a better prognosis in the high LONS group. Stratified analysis of the effect of the categorical variable LONS on CSS and OS revealed that LONS was also an independent predictor, independent of pN stage, pT stage, tumor-node-metastasis stage, site, age, sex, the number of examined lymph nodes, race, preoperative radiotherapy and carcinoembryonic antigen level. CONCLUSION: LONS is associated with improved survival of rectal cancer patients independent of other clinicopathological factors.

Evolutionary Trajectory of the Tet(X) Family: Critical Residue Changes towards High-Level Tigecycline Resistance.

The emergence of the plasmid-mediated high-level tigecycline resistance mechanism Tet(X) threatens the role of tigecycline as the "last-resort" antibiotic in the treatment of infections caused by carbapenem-resistant Gram-negative bacteria. Compared with that of the prototypical Tet(X), the enzymatic activities of Tet(X3) and Tet(X4) were significantly enhanced, correlating with high-level tigecycline resistance, but the underlying mechanisms remain unclear. In this study, we probed the key amino acid changes leading to the enhancement of Tet(X) function and clarified the structural characteristics and evolutionary path of Tet(X) based upon the key residue changes. Through domain exchange and site-directed mutagenesis experiments, we successfully identified five candidate residues mutations (L282S, A339T, D340N, V350I, and K351E), involved in Tet(X2) activity enhancement. Importantly, these 5 residue changes were 100% conserved among all reported high-activity Tet(X) orthologs, Tet(X3) to Tet(X7), suggesting the important role of these residue changes in the molecular evolution of Tet(X). Structural analysis suggested that the mutant residues did not directly participate in the substrate and flavin adenine dinucleotide (FAD) recognition or binding, but indirectly altered the conformational dynamics of the enzyme through the interaction with adjacent residues. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and UV full-wavelength scanning experiments confirmed that each mutation led to an increase in activity without changing the biochemical properties of the Tet(X) enzyme. Further phylogenetic analysis suggested that Riemerella anatipestifer served as an important incubator and a main bridge vector for the resistance enhancement and spread of Tet(X). This study expands the knowledge of the structure and function of Tet(X) and provides insights into the evolutionary relationship between Tet(X) orthologs.IMPORTANCE The newly emerged tigecycline-inactivating enzymes Tet(X3) and Tet(X4), which are associated with high-level tigecycline resistance, demonstrated significantly higher activities in comparison to that of the prototypical Tet(X) enzyme, threatening the clinical efficacy of tigecycline as a last-resort antibiotic to treat multidrug-resistant (MDR) Gram-negative bacterial infections. However, the molecular mechanisms leading to high-level tigecycline resistance remain elusive. Here, we identified 5 key residue changes that lead to enhanced Tet(X) activity through domain swapping and site-directed mutagenesis. Instead of direct involvement with substrate binding or catalysis, these residue changes indirectly alter the conformational dynamics and allosterically affect enzyme activities. These findings further broaden the understanding of the structural characteristics and functional evolution of Tet(X) and provide a basis for the subsequent screening of specific inhibitors and the development of novel tetracycline antibiotics.

Laparoscopic proximal gastrectomy with double-tract reconstruction for upper third gastric cancer.

BACKGROUND: Proximal gastrectomy with double-tract reconstruction (DTR) has been used for upper third gastric cancer as a function-preserving procedure. However, the safety and feasibility of laparoscopic proximal gastrectomy (LPG) with DTR remain uncertain. This study compared open proximal gastrectomy (OPG) with DTR and LPG with DTR for proximal gastric cancer. METHODS: Sixty-four patients who had undergone OPG with DTR and forty-six patients who had undergone LPG with DTR were enrolled in this case-control study. The clinical characteristics, surgical outcomes and postoperative nutrition index were analysed retrospectively. RESULTS: The operation time was significantly longer in the LGP group than in the OPG group (258.3 min vs 205.8 min; p = 0.00). However, the time to first flatus and postoperative hospital stay were shorter in the LPG group [4.0 days vs 3.5 days (p = 0.00) and 10.6 days vs 9.2 days (p = 0.001), respectively]. No significant difference was found between the two groups in the number of retrieved lymph nodes, complications or reflux oesophagitis. The nutrition status was assessed using the haemoglobin, albumin, prealbumin and weight levels from pre-operation to six months after surgery. No significant difference was found between the groups. CONCLUSION: LPG with DTR can be safely performed for proximal gastric cancer patients by experienced surgeons.

Inflammatory bowel disease and risk of gastric, small bowel and colorectal cancer: a meta-analysis of 26 observational studies.

PURPOSE: The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. METHODS: We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle-Ottawa-Scale. RESULTS: Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn's disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. CONCLUSIONS: IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.

RNF115 promotes lung adenocarcinoma through Wnt/ß-catenin pathway activation by mediating APC ubiquitination.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/ß-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear. METHODS: RNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression. RESULTS: We demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/ß-catenin pathway via ubiquitination of adenomatous polyposis coli (APC). CONCLUSION: The current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.

Spread of tet(X5) and tet(X6) genes in multidrug-resistant Acinetobacter baumannii strains of animal origin.

The recent emergence of plasmid-mediated tigecycline resistance gene tet(X) has challenged the clinical effectiveness of tigecycline as a last-resort treatment option. During 2017-2018, 336 fecal samples from sick ducks, pigs, chickens and geese in Guangdong, China, were screened for tet(X)-positive Acinetobacter baumannii strains. Their activities on tetracyclines were determined by microbiological degradation and mass spectrometry, followed by susceptibility testing, sequence typing, gene transfer, molecular location and genomic DNA sequencing analyses. A total of 10 tet(X)-positive A. baumannii strains were isolated from ducks and chickens, including eight plasmid-borne tet(X5)-positive and two chromosomal tet(X6)-positive isolates. All of them exhibited good degradation activities on tetracyclines by hydroxylation at C11a and were multidrug-resistant to tigecycline, tetracycline, florfenicol, ciprofloxacin and trimethoprim/sulfamethoxazole. Genetically, they belonged to two sequence types (ST355, n = 8; ST1980, n = 2) that were consistent with their pulsotypes, revealing a clonal spread of ST355 A. baumannii. An ISCR2- or IS26-mediated tet(X) transposition structure, homologous to those of clinical A. baumannii strains, was also identified and ISCR2 could transfer tet(X5) into the recipient Acinetobacter baylyi ADP1 at a frequency of (1.8 ± 0.3)×10-6. Therefore, more efforts are needed to evaluate the clinical impact of these tigecycline resistance genes.

Genetic diversity and characteristics of high-level tigecycline resistance Tet(X) in Acinetobacter species.

BACKGROUND: The recent emergence and dissemination of high-level mobile tigecycline resistance Tet(X) challenge the clinical effectiveness of tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens. Although tet(X) has been found in various bacterial species, less is known about phylogeographic distribution and phenotypic variance of different genetic variants. METHODS: Herein, we conducted a multiregional whole-genome sequencing study of tet(X)-positive Acinetobacter isolates from human, animal, and their surrounding environmental sources in China. The molecular and enzymatic features of tet(X) variants were characterized by clonal expression, microbial degradation, reverse transcription, and gene transfer experiments, while the tet(X) genetic diversity and molecular evolution were explored by comparative genomic and Bayesian evolutionary analyses. RESULTS: We identified 193 tet(X)-positive isolates from 3846 samples, with the prevalence ranging from 2.3 to 25.3% in nine provinces in China. The tet(X) was broadly distributed in 12 Acinetobacter species, including six novel species firstly described here. Besides tet(X3) (n = 188) and tet(X4) (n = 5), two tet(X5) variants, tet(X5.2) (n = 36) and tet(X5.3) (n = 4), were also found together with tet(X3) or tet(X4) but without additive effects on tetracyclines. These tet(X)-positive Acinetobacter spp. isolates exhibited 100% resistance rates to tigecycline and tetracycline, as well as high minimum inhibitory concentrations to eravacycline (2-8 µg/mL) and omadacycline (8-16 µg/mL). Genetic analysis revealed that different tet(X) variants shared an analogous ISCR2-mediated transposon structure. The molecular evolutionary analysis indicated that Tet(X) variants likely shared the same common ancestor with the chromosomal monooxygenases that are found in environmental Flavobacteriaceae bacteria, but sequence divergence suggested separation ~ 9900 years ago (7887 BC), presumably associated with the mobilization of tet(X)-like genes through horizontal transfer. CONCLUSIONS: Four tet(X) variants were identified in this study, and they were widely distributed in multiple Acinetobacter spp. strains from various ecological niches across China. Our research also highlighted the crucial role of ISCR2 in mobilizing tet(X)-like genes between different Acinetobacter species and explored the evolutionary history of Tet(X)-like monooxygenases. Further studies are needed to evaluate the clinical impact of these mobile tigecycline resistance genes.