Study on Oleum cinnamomi Inhibiting Cutibacterium acnes and Its Covalent Inhibition Mechanism.

Oleum cinnamomi (OCM) is a volatile component of the Cinnamomum cassia Presl in the Lauraceae family, which displays broad-spectrum antibacterial properties. It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 µg/mL and 180 µg/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.

A versatile dilution-treatment-detection microfluidic chip platform for rapid In vitro lung cancer drug combination sensitivity evaluation.

Combination drug therapy represents an effective strategy for treating certain drug-resistant and intractable cancer cases. However, determining the optimal combination of drugs and dosages is challenging due to clonal diversity in patients' tumors and the lack of rapid drug sensitivity evaluation methods. Microfluidic technology offers promising solutions to this issue. In this study, we propose a versatile microfluidic chip platform capable of integrating all processes, including dilution, treatment, and detection, for in vitro drug sensitivity assays. This platform innovatively incorporates several modules, including automated discrete drug logarithmic concentration generation, on-chip cell perfusion culture, and parallel drug treatments of cancer cell models. Moreover, it is compatible with microplate readers or high-content imaging systems for swift detection and automated monitoring, simplifying on-chip drug evaluation. Proof of concept is demonstrated by assessing the in vitro potency of two drugs, cisplatin, and etoposide, against the lung adenocarcinoma A549 cell line, under both single-drug and combination treatment conditions. The findings reveal that, compared to conventional microplate approaches with static cultivation, this on-chip automated perfusion bioassays yield comparable IC50 values with lower variation and a 50 % reduction in drug preparation time. This versatile dilution-treatment-detection microfluidic platform offers a promising tool for rapid and precise drug assessments, facilitating in vitro drug sensitivity evaluation in personalized cancer chemotherapy.

Screening of co-expressed genes in hypopharyngeal carcinoma with esophageal carcinoma based on RNA sequencing and Clinical Research.

To explore the hub comorbidity genes and potential pathogenic mechanisms of hypopharyngeal carcinoma with esophageal carcinoma, and evaluate their diagnostic value for hypopharyngeal carcinoma with co-morbid esophageal carcinoma. We performed gene sequencing on tumor tissues from 6 patients with hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma (hereafter referred to as "group A") and 6 patients with pure hypopharyngeal squamous cell carcinoma (hereafter referred to as "group B"). We analyzed the mechanism of hub genes in the development and progression of hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma through bioinformatics, and constructed an ROC curve and Nomogram prediction model to analyze the value of hub genes in clinical diagnosis and treatment. 44,876 genes were sequenced in 6 patients with group A and 6 patients with group B. Among them, 76 genes showed significant statistical differences between the group A and the group B.47 genes were expressed lower in the group A than in the group B, and 29 genes were expressed higher. The top five hub genes were GABRG2, CACNA1A, CNTNAP2, NOS1, and SCN4B. GABRG2, CNTNAP2, and SCN4B in the hub genes have high diagnostic value in determining whether hypopharyngeal carcinoma patients have combined esophageal carcinoma (AUC: 0.944, 0.944, 0.972). These genes could possibly be used as potential molecular markers for assessing the risk of co-morbidity of hypopharyngeal carcinoma combined with esophageal carcinoma.

Quercetin inhibits chronic stress-mediated progression of triple-negative breast cancer by blocking ß2-AR/ERK1/2 pathway.

Chronic stress-mediated sustained release of neurotransmitters, which ultimately leads to the activation of ß2-adrenergic receptor (ß2-AR) signaling, is one of the most important reasons for triple-negative breast cancer (TBNC) progression. Quercetin (Que) has been proven to have the advantage of ameliorating stress psychological disorder. Our present study aimed to investigate the effect of Que on tumor growth and metastasis in TNBC xenograft mice undergoing stress, and to explore its underlying mechanisms. We first evaluated the effect of Que on the progression of TNBC in nude mice in vivo. The results showed that, Que could inhibit chronic stress-induced TNBC growth and occurrence of lung metastasis. We subsequently employed epinephrine (E) as a representative of stress hormone to investigate its possible mechanism in vitro. The results showed that, Que could inhibit E-mediated proliferation and migration of TNBC cells by blocking ß2-AR/ERK1/2 pathway. In conclusion, our data demonstrated that Que could inhibit chronic stress-induced ERK1/2 activity in TNBC cells, and thereby weakening the potential for TNBC growth and metastasis.

Uncommon P1 Anchor-featured Viral T Cell Epitope Preference within HLA-A*2601 and HLA-A*0101 Individuals.

The individual HLA-related susceptibility to emerging viral diseases such as COVID-19 underscores the importance of understanding how HLA polymorphism influences peptide presentation and T cell recognition. Similar to HLA-A*0101, which is one of the earliest identified HLA alleles among the human population, HLA-A*2601 possesses a similar characteristic for the binding peptide and acts as a prevalent allomorph in HLA-I. In this study, we found that, compared with HLA-A*0101, HLA-A*2601 individuals exhibit distinctive features for the T cell responses to SARS-CoV-2 and influenza virus after infection and/or vaccination. The heterogeneous T cell responses can be attributed to the distinct preference of HLA-A*2601 and HLA-A*0101 to T cell epitope motifs with negative-charged residues at the P1 and P3 positions, respectively. Furthermore, we determined the crystal structures of the HLA-A*2601 complexed to four peptides derived from SARS-CoV-2 and human papillomavirus, with one structure of HLA-A*0101 for comparison. The shallow pocket C of HLA-A*2601 results in the promiscuous presentation of peptides with "switchable" bulged conformations because of the secondary anchor in the median portion. Notably, the hydrogen bond network formed between the negative-charged P1 anchors and the HLA-A*2601-specific residues lead to a "closed" conformation and solid placement for the P1 secondary anchor accommodation in pocket A. This insight sheds light on the intricate relationship between HLA I allelic allomorphs, peptide binding, and the immune response and provides valuable implications for understanding disease susceptibility and potential vaccine design.

Preparation, structural characterization, biological activity, and nutritional applications of oligosaccharides.

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.

Neutrophil extracellular traps mediate cardiomyocyte ferroptosis via the Hippo-Yap pathway to exacerbate doxorubicin-induced cardiotoxicity.

Doxorubicin-induced cardiotoxicity (DIC), which is a cardiovascular complication, has become the foremost determinant of decreased quality of life and mortality among survivors of malignant tumors, in addition to recurrence and metastasis. The limited ability to accurately predict the occurrence and severity of doxorubicin-induced injury has greatly hindered the prevention of DIC, but reducing the dose to mitigate side effects may compromise the effective treatment of primary malignancies. This has posed a longstanding clinical challenge for oncologists and cardiologists. Ferroptosis in cardiomyocytes has been shown to be a pivotal mechanism underlying cardiac dysfunction in DIC. Ferroptosis is influenced by multiple factors. The innate immune response, as exemplified by neutrophil extracellular traps (NETs), may play a significant role in the regulation of ferroptosis. Therefore, the objective of this study was to investigate the involvement of NETs in doxorubicin-induced cardiomyocyte ferroptosis and elucidate their regulatory role. This study confirmed the presence of NETs in DIC in vivo. Furthermore, we demonstrated that depleting neutrophils effectively reduced the occurrence of doxorubicin-induced ferroptosis and myocardial injury in DIC. Additionally, our findings showed the pivotal role of high mobility group box 1 (HMGB1) as a critical molecule implicated in DIC and emphasized its involvement in the modulation of ferroptosis subsequent to NETs inhibition. Mechanistically, we obtained preliminary evidence suggesting that doxorubicin-induced NETs could modulate yes-associated protein (YAP) activity by releasing HMGB1, which subsequently bound to toll like receptor 4 (TLR4) on the cardiomyocyte membrane, thereby influencing cardiomyocyte ferroptosis in vitro. Our findings suggest that doxorubicin-induced NETs modulate cardiomyocyte ferroptosis via the HMGB1/TLR4/YAP axis, thereby contributing to myocardial injury. This study offers a novel approach for preventing and alleviating DIC by targeting alterations in the immune microenvironment.

Correlation between PD-1 and sPD-L1 expression levels in peripheral blood of DLBCL patients and their clinicopathological characteristics.

Molecular pathology and clinical characteristics play a crucial role in guiding treatment selection and predicting the prognosis of diffuse large B-cell lymphoma (DLBCL). The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have emerged as pivotal regulators of immune checkpoints in cancer. The objectives of this study are to investigate the correlation between the expression levels of PD-1 and soluble PD-L1 (sPD-L1) in the peripheral blood of DLBCL patients, analyze their clinicopathological characteristics, and identify the optimal beneficiary group for PD-1/PD-L1 blockade. Peripheral blood samples were collected from 36 DLBCL patients before their initial treatment at Shandong Cancer Hospital between December 2018 and July 2019. The expression levels of PD-1 and sPD-L1 were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The clinicopathological characteristics, including age, sex, Ann Arbor stage, International Prognostic Index (IPI) score, response to treatment, etc., were recorded for each patient. The surface expression of PD-1 on peripheral blood T cells was significantly higher in DLBCL patients compared to healthy controls. There was a significant association between elevated PD-1 expression levels and the advanced Ann Arbor stage (P=0.0153) as well as the B group (P=0.0184). Higher sPD-L1 levels were associated with the GCB subtype according to Hans's classification (P=0.0435). The expression levels of PD-1 and sPD-L1 in the peripheral blood of DLBCL patients are significantly correlated with advanced disease stage, B group, and GCB subtype according to Hans's classification. This suggests that the PD-1/PD-L1 axis play a critical role in specific subgroups of DLBCL. Targeting this axis could serve as a potential therapeutic strategy to enhance the clinical outcomes of DLBCL patients. Further studies are necessary to explore the prognostic implications of PD-1 and sPD-L1 expression levels in DLBCL patients.

Ureter Metastasis From Colorectal Cancer Revealed on 18 F-FDG PET/CT.

ABSTRACT: The involvement of the ureter as a site of metastasis of colorectal cancer is quite rare. Here we present FDG PET/CT findings of the right ureter metastasis from colon cancer in a patient after colectomy 6 years ago. 18 F-FDG PET/CT showed increased 18 F-FDG uptake in the right ureter with SUV max of 4.3. The pathology and immunohistochemistry confirmed the diagnosis of ureter metastasis from colon cancer.

Integrating network pharmacology and experimental verification to investigate the pharmacological mechanisms of Buzhong Yiqi decoction in the treatment of non-small cell lung cancer.

Among all types of cancers, non-small cell lung cancer (NSCLC) exhibits the highest mortality rate with a five-year survival rate below 17% for patients. The Buzhong Yiqi decoction (BZYQD), traditional Chinese medicine (TCM) formula, has been reported to exhibit clinical efficacy in the treatment of NSCLC. Nevertheless, the underlying molecular mechanism remains elusive. This study aimed to assess the mechanistic actions exerted by BZYQD against NSCLC using network pharmacological analysis and experimental validation. The public databases were searched for active compounds in BZYQD, their potential targets, and NSCLC-related targets. The protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the core targets and signaling pathways of BZYQD against NSCLC. After screening, this study validated the results of predictions through in vitro experiments and public databases. We found 192 common targets between BZYQD and NSCLC. KEGG analysis showed that the anti-NSCLC effects of BZYQD were mediated through the PI3K-AKT signaling pathway. The results of in vitro experiment indicated that BZYQD could inhibit cell viability and proliferation of A549 and H1299 cells apart from inducing cell apoptosis. In addition, western blot results substantiated that BZYQD could treat NSCLC by inhibiting the activation of the PI3K-AKT signaling pathway. The current study investigated the pharmacological mechanism of BZYQD against NSCLC via network pharmacology and in vitro analyses. Overall, the results revealed that BZYQD could be a promising therapeutic agent for the treatment of NSCLC in the future. Still, more experimental investigations are needed to confirm the applicability of BZYQD for clinical trials.

Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Radix Astragali against hypopharyngeal carcinoma.

To explore the anti-tumor effects of Radix Astragali on hypopharyngeal carcinoma and its mechanism. We have bioinformatically analyzed the potential targets of Radix Astragali and predicted the molecular mechanism of Radix Astragali treating of hypopharyngeal carcinoma. The binding process of the hub targets that could prolong the survival time of hypopharyngeal cancer patients with Radix Astragali was simulated by molecular docking. The results showed that 17 out of 36 hub targets could effectively improve the 5-year survival rate of hypopharyngeal cancer patients. Radix Astragali acts on hypopharyngeal carcinoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways and is expected to become a drug for treating and prolonging hypopharyngeal carcinoma patients' survival time.

HPV16 E6 promoting cervical cancer progression through down-regulation of miR-320a to increase TOP2A expression.

BACKGROUND: Cervical cancer (CC) has become the fourth most common cancer worldwide and it is mainly caused by the infection of human papillomavirus (HPV), especially high-risk HPV16. Aberrant miRNA expression in CC is closely related to HPV16 infection, and the regulation of HPV16 E6 expression can affect a variety of miRNA expression. This study aims to exploring the miRNAs involved in E6 regulation in CC. METHODS: Our study screened differentially expressed miRNAs in cervical cells of HPV16 infected and uninfected cervical cancer patients by analyzing the GSE81137 dataset of the gene expression omnibus database (GEO), and identified miR-320a that plays an anti-tumor role and is associated with good prognosis of cervical cancer. Explore the effect of HPV16 E6 on the expression of miR-320a in cervical cancer, and verify whether HPV16 E6 regulates the downstream target gene TOP2A expression through miR-320a, thereby affecting cervical cancer cell proliferation, apoptosis, migration, invasion, and EMT in vitro and in vivo. RESULTS: The bioinformatic methods selected the miR-320a, which was differentially expressed in cervical cells from HPV16-infected patients compared to uninfected patients. We further demonstrated that miR-320a level was regulated by HPV16 E6, which promoted the CC cell proliferation, migration, invasion, and inhibited apoptosis. In addition, we predicted the downstream target genes of miR-320a and confirmed that TOP2A was one of its targeting proteins. Moreover, HPV16 E6 promoted the TOP2A expression in CC cells through down-regulating miR-320a, leading to promoting CC development. CONCLUSIONS: We confirmed that HPV16 E6 promoted the TOP2A expression through down-regulation of miR-320a, thus promoting CC development, and the HPV16 E6/miR-320a/TOP2A axis may perform as a potential target for CC treatment.

A systematic strategy for investigating the pharmacological effects and mechanism of traditional Chinese medicinal formula: Guilin Xiguashuang as a case.

BACKGROUND: Traditional Chinese medicinal formula (TCMF) has specific advantages in treating diseases. However, the pharmacological effects and mechanism of TCMF composed of traditional Chinese medicines (TCM) with unclear active components or targets have not yet been fully elucidated. OBJECTIVES: This research proposed a strategy for elucidating the pharmacological effects and mechanism to address this issue systematically. METHODS: With Guilin Xiguashuang (GLXGS) taken as a case, this study newly provided the multi-level assays, which decomposes TCMF into components, TCM, and TCMF levels. The main pharmacological effects were acquired through a comprehensive analysis based on the active components, pharmacological effects of TCM, and clinical efficacy of TCMF, respectively. The core targets and pathways were further identified and verified to elucidate the mechanism. RESULTS: The main pharmacological effects of GLXGS were anti-inflammatory, analgesic, antibacterial, immunoregulatory, and wound healing. Moreover, the mechanism analysis demonstrated that GLXGS was involved in the regulation of NF-κB and VEGF signaling pathways and core targets, such as IL-6 and TNF-α. Finally, unproven immunomodulatory and anti-inflammatory mechanism were verified using RAW264.7 and THP-1 cells. GLXGS was verified to down-regulate IL-6, IL-1ß, TNF-α, and CD86 in lipopolysaccharides-stimulated RAW264.7 cells, while enhancing polarization in both RAW264.7 and THP-1 cells, which were consistent with analysis results. CONCLUSION: The present research provides a systematic strategy for the pharmacological effect prediction and mechanism analysis of TCMF, which is of great significance for studying complex TCMF.

CT-Based Radiomics for the Preoperative Prediction of Occult Peritoneal Metastasis in Epithelial Ovarian Cancers.

RATIONALE AND OBJECTIVES: The objective of this study was to develop a comprehensive combined model for predicting occult peritoneal metastasis (OPM) in epithelial ovarian cancers (EOCs) using radiomics features derived from computed tomography (CT) and clinical-radiological predictors. MATERIALS AND METHODS: A total of 224 patients with EOCs were randomly divided into training dataset (N = 156) and test dataset (N = 86). Five clinical factors and seven radiological features were collected. The radiomics features were extracted from CT images of each patient. Multivariate logistic regression was employed to construct clinical and radiological models. The correlation analysis and least absolute shrinkage and selection operator algorithm were used to select radiomics features and build radiomics model. The important clinical, radiological factors, and radiomics features were integrated into a combined model by multivariate logistic regression. Receiver operating characteristics curve with area under the curve (AUC) were used to evaluate and compare predictive performance. RESULTS: Carbohydrate antigen 125 (CA-125) and human epididymal protein 4 (HE-4) were independent clinical predictors. Laterality, thickened septa and margin were independent radiological predictors. In the training dataset, the AUCs for the clinical, radiological and radiomics models in evaluating OPM were 0.759, 0.819, and 0.830, respectively. In the test dataset, the AUCs for these models were 0.846, 0.835, and 0.779, respectively. The combined model outperformed other models in both the training and the test datasets with AUCs of 0.901 and 0.912, respectively. Decision curve analysis indicated that the combined model yielded a higher net benefit compared to the other models. CONCLUSION: The combined model, integrating radiomics features with clinical and radiological predictors exhibited improved accuracy in predicting OPM in EOCs.

FOXA1 O-GlcNAcylation-mediated transcriptional switch governs metastasis capacity in breast cancer.

FOXA1, a transcription factor involved in epigenetic reprogramming, is crucial for breast cancer progression. However, the mechanisms by which FOXA1 achieves its oncogenic functions remain elusive. Here, we demonstrate that the O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation) of FOXA1 promotes breast cancer metastasis by orchestrating the transcription of numerous metastasis regulators. O-GlcNAcylation at Thr432, Ser441, and Ser443 regulates the stability of FOXA1 and promotes its assembly with chromatin. O-GlcNAcylation shapes the FOXA1 interactome, especially triggering the recruitment of the transcriptional repressor methyl-CpG binding protein 2 and consequently stimulating FOXA1 chromatin-binding sites to switch to chromatin loci of adhesion-related genes, including EPB41L3 and COL9A2. Site-specific depletion of O-GlcNAcylation on FOXA1 affects the expression of various downstream genes and thus inhibits breast cancer proliferation and metastasis both in vitro and in vivo. Our data establish the importance of aberrant FOXA1 O-GlcNAcylation in breast cancer progression and indicate that targeting O-GlcNAcylation is a therapeutic strategy for metastatic breast cancer.

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

Isethionate is an intermediate in the degradation of sulfoacetate by the human gut pathobiont Bilophila wadsworthia.

The obligately anaerobic sulfite-reducing bacterium Bilophila wadsworthia is a common human pathobiont inhabiting the distal intestinal tract. It has a unique ability to utilize a diverse range of food- and host-derived sulfonates to generate sulfite as a terminal electron acceptor (TEA) for anaerobic respiration, converting the sulfonate sulfur to H2S, implicated in inflammatory conditions and colon cancer. The biochemical pathways involved in the metabolism of the C2 sulfonates isethionate and taurine by B. wadsworthia were recently reported. However, its mechanism for metabolizing sulfoacetate, another prevalent C2 sulfonate, remained unknown. Here, we report bioinformatics investigations and in vitro biochemical assays that uncover the molecular basis for the utilization of sulfoacetate as a source of TEA (STEA) for B. wadsworthia, involving conversion to sulfoacetyl-CoA by an ADP-forming sulfoacetate-CoA ligase (SauCD), and stepwise reduction to isethionate by NAD(P)H-dependent enzymes sulfoacetaldehyde dehydrogenase (SauS) and sulfoacetaldehyde reductase (TauF). Isethionate is then cleaved by the O2-sensitive isethionate sulfolyase (IseG), releasing sulfite for dissimilatory reduction to H2S. Sulfoacetate in different environments originates from anthropogenic sources such as detergents, and natural sources such as bacterial metabolism of the highly abundant organosulfonates sulfoquinovose and taurine. Identification of enzymes for anaerobic degradation of this relatively inert and electron-deficient C2 sulfonate provides further insights into sulfur recycling in the anaerobic biosphere, including the human gut microbiome.

A Variant of the Sulfoglycolytic Transketolase Pathway for the Degradation of Sulfoquinovose into Sulfoacetate.

Sulfoquinovose (SQ, 6-deoxy-6-sulfo-glucose) constitutes the polar head group of plant sulfolipids and is one of the most abundantly produced organosulfur compounds in nature. Degradation of SQ by bacterial communities contributes to sulfur recycling in many environments. Bacteria have evolved at least four mechanisms for glycolytic degradation of SQ, termed sulfoglycolysis, producing C3 sulfonate (dihydroxypropanesulfonate and sulfolactate) and C2 sulfonate (isethionate) by-products. These sulfonates are further degraded by other bacteria, leading to the mineralization of the sulfonate sulfur. The C2 sulfonate sulfoacetate is widespread in the environment and is also thought to be a product of sulfoglycolysis, although the mechanistic details are yet unknown. Here, we describe a gene cluster in an Acholeplasma sp., from a metagenome derived from deeply circulating subsurface aquifer fluids (GenBank accession no. QZKD01000037), encoding a variant of the recently discovered sulfoglycolytic transketolase (sulfo-TK) pathway that produces sulfoacetate instead of isethionate as a by-product. We report the biochemical characterization of a coenzyme A (CoA)-acylating sulfoacetaldehyde dehydrogenase (SqwD) and an ADP-forming sulfoacetate-CoA ligase (SqwKL), which collectively catalyze the oxidation of the transketolase product sulfoacetaldehyde into sulfoacetate, coupled with ATP formation. A bioinformatics study revealed the presence of this sulfo-TK variant in phylogenetically diverse bacteria, adding to the variety of mechanisms by which bacteria metabolize this ubiquitous sulfo-sugar. IMPORTANCE Many bacteria utilize environmentally widespread C2 sulfonate sulfoacetate as a sulfur source, and the disease-linked human gut sulfate- and sulfite-reducing bacteria can use it as a terminal electron receptor for anaerobic respiration generating toxic H2S. However, the mechanism of sulfoacetate formation is unknown, although it has been proposed that sulfoacetate originates from bacterial degradation of sulfoquinovose (SQ), the polar head group of sulfolipids present in all green plants. Here, we describe a variant of the recently discovered sulfoglycolytic transketolase (sulfo-TK) pathway. Unlike the regular sulfo-TK pathway that produces isethionate, our biochemical assays with recombinant proteins demonstrated that a CoA-acylating sulfoacetaldehyde dehydrogenase (SqwD) and an ADP-forming sulfoacetate-CoA ligase (SqwKL) in this variant pathway collectively catalyze the oxidation of the transketolase product sulfoacetaldehyde into sulfoacetate, coupled with ATP formation. A bioinformatics study revealed the presence of this sulfo-TK variant in phylogenetically diverse bacteria and interpreted the widespread existence of sulfoacetate.