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DNA repair and autophagy are distinct biological processes vital for cell survival. Although autophagy helps maintain genome stability, there is no evidence of its direct role in the repair of DNA lesions. We discovered that lysosomes process topoisomerase 1 cleavage complexes (TOP1cc) DNA lesions in vertebrates. Selective degradation of TOP1cc by autophagy directs DNA damage repair and cell survival at clinically relevant doses of topoisomerase 1 inhibitors. TOP1cc are exported from the nucleus to lysosomes through a transient alteration of the nuclear envelope and independent of the proteasome. Mechanistically, the autophagy receptor TEX264 acts as a TOP1cc sensor at DNA replication forks, triggering TOP1cc processing by the p97 ATPase and mediating the delivery of TOP1cc to lysosomes in an MRE11-nuclease- and ATR-kinase-dependent manner. We found an evolutionarily conserved role for selective autophagy in DNA repair that enables cell survival, protects genome stability, and is clinically relevant for colorectal cancer patients.

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Environmental science studies from the past decade have emphasized that microplastics in aquatic environments are mostly caused by domestic laundering of synthetic textiles. Although many studies have explored the microfiber release behavior of fabrics washed in laundry, attempts to witness microfiber release from sewing threads, which are an inevitable part of any finished garment, are meager. With this research gap, this study attempted to analyze the potential of sewing threads to release microfibers during washing and the extent to which they can contribute to the overall microfiber release during domestic laundering. The study's findings revealed an average release of 2.65 ± 0.70 (n=33) microfibers/m from the sewing thread sewn on the fabric during laundering. The sewing process was noted to cause damage to the sewing thread, which led to a comparatively higher microfiber release (∼114%) compared with the sewing threads that were washed before sewing. Among the selected sewing threads, higher microfiber emissions were reported with spun threads, followed by twistless filaments, and twisted filament threads. The results showed that coarser sewing threads with higher Tex values released more microfibers than finer Tex threads. Compared to the 20Tex spun thread, the 80Tex spun thread showed a 22-150% increase in microfiber release. In the case of filament sewing thread, a similar impact was noted, whereas the role of twist was found to be efficient in reducing microfiber emission. Compared to the untwisted filaments, the ply twisted filaments exhibited approximately 76% lower microfiber emissions. The findings of this study showed that sewing thread contributed approximately 1.09% of the total microfiber emissions from apparel during laundry.

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The Synaptotagmin-like mitochondrial-lipid binding protein (SMP) domain is found in a group of ER-resident lipid transfer proteins that are recruited to membrane contact sites (MCSs) by adaptors. Deciphering the molecular basis underlying the recruitment of SMP proteins to specific MCS sheds light not only on their cellular localization but also on their biological functions at these sites. Here we summarize recent advances in SMP domain-containing lipid transfer proteins, focusing on a recent study showing the localization, regulation and cellular function of a specific SMP protein named testis expressed protein 2 (Tex2). TMEM55, a potential PIP phosphatase on late endosome/lysosomal (LE/lys) membranes, was identified as an adaptor that enables the recruitment of Tex2 to ER- LE/lys MCS. In addition, we have summarized several important questions about the regulation and physiological functions of Tex2 that remained unanswered.

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In situations involving continuous exposure to antigens, such as chronic infections or cancer, antigen-specific CD8+ T cells can become dysfunctional or exhausted. This change is marked by increased expression levels of inhibitory receptors (PD-1 and Tim-3). Stem-like progenitor exhausted (Tpex) cells, a subset of exhausted cells that express TCF-1 and are mainly found in the lymph nodes, demonstrate the ability to self-renew and exhibit a high rate of proliferation. Tpex cells can further differentiate into transitional intermediate exhausted (Tex-int) cells and terminally exhausted (Tex-term) cells. Alternatively, they can directly differentiate into Tex-term cells. Tpex cells are the predominant subset that respond to immune checkpoint inhibitors (ICI), making them a prime candidate for improving the efficacy of ICI therapy. This review article aimed to present the latest developments in the field of Tpex formation, expansion, and differentiation in the context of cancer, as well as their responses to ICIs in cancer immunotherapy. Consequently, it may be possible to develop novel treatments that exclusively target Tpex cells, thus improving overall treatment outcomes. KEY POINTS: Tpex cells are located in lymph nodes and TLS. Several pathways control the differentiation trajectories of Tpex cells, including epigenetic factors, transcription factors, cytokines, age, sex, etc.

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Background: Our review of 12 articles for this perspective showed the frequency of intraoperative thoracic and/or lumbar CSF fistulas/dural tears (DT) ranged from 2.6% - 8% for primary surgical procedures. Delayed postoperative CSF leak/DT were also diagnosed in 0.83% (17/2052 patients) to 14.3% (2/14 patients) of patients undergoing thoracic and/or lumbar procedures. Further, the rate of recurrent postoperative CSF leaks/DT varied from 13.3% (2/15 patients) to 33.3% (4/12 patients). Methods: Intraoperative, postoperative delayed, and recurrent postoperative traumatic postsurgical thorac CSF leaks/DT can be limited by performing initially sufficient operative decompressions and/or decompressions/fusions (i.e., utilizing adequate open exposures vs. inadequate minimally invasive (MI) approaches). The incidence of CSF leaks/DT can be further reduced by spine surgeons' utilization of operating microscopes, and their avoiding routine attempts at total synovial cyst excision and/or complete resection of hypertrophied/ossified yellow ligament in the presence of significant dural adhesions. Results: Multiple CSF leak/CT repair techniques included; using interrupted, non-resorbable sutures for direct dural repairs (i.e. 7-0 Gore-Tex sutures where the suture is larger than the needle thus plugging needle holes), and adding where needed muscle patch grafts, microfibrillar collagen, the rotation of Multifidus muscle pedicle flaps, fibrin sealants (FS)/fibrin glues (FG), lumbar drains (LD), and/or lumbo-peritoneal (LP) shunts. Conclusion: Intraoperative, postopertive delayed, and/or recurrent postoperative thorac and/or lumbar traumatic surgical CSF leaks can be reduced by choosing to initially perform the appropriately extensive open operative decompressions and/or decompresssions/fusions. It is critical to use an operating microscope, non-resorbable interrupted sutures, and where necessary, muscle patch grafts, microfibrillar collagen, the rotation of Multifidus Muscle Pedicle Flaps, FS/FG, LD, and/or LP shunts.

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BACKGROUND: Colorectal cancer (CRC) is one of the most frequently encountered malignant tumors in clinical settings. Proteins encoded by the testis-expressed gene 14 (TEX14) are imperative for spermatogenesis, necessitating intercellular bridges between germ cells. Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells. Recombinant A disintegrin and metalloprotease 17 (ADAM17) is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane. We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging, invasion, and metastasis of CRC. AIM: To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging, invasion, and metastasis. METHODS: We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023. For each patient, one sample of cancer tissue and one sample of adjacent normal tissue were harvested. Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17. Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions. Clinical pathological features of neoplasm staging, invasion, and metastasis were collected, and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated. RESULTS: The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues. The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93% and 77.91%, respectively. There were no significant differences in age, sex, pathological type, and tumor diameter between TEX14 and ADAM17-positive and -negative patients. Patients with higher tumor differentiation degree, deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17. Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without. Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging, invasion, and metastasis. CONCLUSION: TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients, and their high expressions were associated with tumor staging, invasion, and metastasis.

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Background: Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA. Methods: We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC. Results: We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property. To define the heterogeneity of tumours and their associated microenvironments, we observe greater tumour diversity in H-ChC than HCC and iCCA. H-ChC exhibits weaker immune cell infiltration and greater CD8+ exhausted T cell (Tex) dysfunction than HCC and iCCA. Then we defined two broad cell states of 6,852 CD8+ Tex cells: GZMK+ CD8+ Tex cells and terminal CD8+ Tex cells. GZMK+ CD8+ Tex cells exhibited higher infiltration of after treatment in H-ChC, the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy, which indicated that H-ChC might be more sensitive than HCC or iCCA to immunotherapy. Conclusions: In this paper, H-ChC was explored, hoping to contribute to the study of mixed tumours in other cancers.

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BACKGROUND: Dislocated IOL exchange conventionally involves manipulation within the anterior chamber which risks secondary injury to anterior chamber structures. We describe and evaluate a 4-haptic IOL rescue technique that avoids entering the anterior chamber and thus minimizes post operative inflammation, astigmatism and recovery time relative to conventional IOL explantation and replacement techniques. METHODS: Retrospective, non-randomized, interventional study of all patients undergoing 4-haptic IOL rescue performed by two independent vitreoretinal surgeons at a single UK centre over two years. SURGICAL TECHNIQUE: A limited peritomy is performed with four 25-gauge scleral ports placed to enable use of two forceps, an infusion and a chandelier. A further four 27-gauge sclerotomies are symmetrically placed on the nasal and temporal sclera at 3 mm from the limbus with a 5 mm vertical separation on either side. A pars plana vitrectomy is performed followed by chandelier illuminated, bimanual cleaning of the dislocated IOL using 27-gauge serrated forceps. Gore-tex sutures are threaded through the IOL islets within the vitreous cavity and externalized through the sclerotomies for scleral re-fixation followed by conjunctival closure. RESULTS: Seven patients underwent IOL recycling with Gore-Tex suture scleral re-fixation. All procedures were successful in repositioning the IOLs, with all patients satisfied with post-operative outcome. Mean (standard deviation) time to IOL dislocation was 13 (3) years. Median visual acuity significantly improved post-operatively from 0.85 logMAR (Interquartile Range [IQR]: 0.2-2.1) to 0.07 (0.02-0.60) logMAR (p = 0.02). No significant post-operative complications were noted apart from persistent cystoid macular oedema in one patient non-compliant with post-operative treatment. CONCLUSIONS: Transscleral refixation using Gore-Tex suture is an effective, safe and practical approach in the management of dislocated 4-piece IOLs.

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The Gore-Tex® polytetrafluoroethylene patch is one of the most used prostheses for diaphragm, vessel, and pericardial reconstruction. It is strong, flexible, and relatively inexpensive and can be fitted to match the size of the resected area. In addition, it can be used to reconstruct the pericardium and diaphragm following resection to treat diffuse malignant pleural mesothelioma or repair large hiatal hernias. However, the use of polytetrafluoroethylene for hepatocellular carcinoma with diaphragmatic and pericardial invasion has not yet been reported. We report the case of a 72-year-old man with hepatocellular carcinoma with diaphragmatic and pericardial invasion. Subsequently, laparotomic liver subsegmentectomy of segment 3 and resection of the diaphragm and pericardium were performed. The defects were successfully reconstructed using the polytetrafluoroethylene patch, without postoperative complications. This is the first report describing a case of invasive liver malignancy that required simultaneous diaphragmatic and pericardial reconstruction using a polytetrafluoroethylene patch, indicating that the polytetrafluoroethylene patch could effectively and directly treat invasive liver malignancies.

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BACKGROUND: Globally, breast cancer in women is the fifth leading cause of cancer death. There is an urgent need to explore the molecular mechanism of breast cancer proliferation and metastasis. METHOD: TCGA database analysis was used to analyze genes expression in breast cancer and normal samples and the association between gene expression and prognosis. Immunohistochemical staining, qPCR and western blotting was sued to detected gene expression. The cell function tests were conducted to investigate the effects of TEX19 and CDK4 with abnormal expression on cell proliferation, migration, apoptosis, cell cycle, and colony formation. Bioinformatics analysis methods combined with CHX tracking experiment and Co-IP experiment were performed to screen and verify the downstream molecule and regulatory mechanism of TEX19. Besides, subcutaneous tumorigenesis model in nude mice was constructed. RESULTS: TEX19 was significantly upregulated in breast cancer, and the TEX19 level was related to tumor invasion and prognosis. TEX19 knockdown inhibited the proliferation and migration of breast cancer cells, increased cell apoptosis, and blocked the cell cycle in the G2 phase. Besides, TEX19 suppressed the growth of tumors in the body. Mechanically, TEX19 upregulated the level of CDK4 protein, which depended on the E3 ubiquitin ligase SKP2. Specifically, TEX19 knockdown and SKP2 protein overexpression destroyed the stability of CDK4 protein and enhanced the ubiquitination of CDK4 protein. Additionally, CDK4 knockdown inhibited the proliferation, migration, and colony formation of breast cancer cells, and alleviated the promotion of TEX19 overexpression on the proliferation and migration of breast cancer cell. CONCLUSION: TEX19 and CDK4 were upregulated in breast cancer, and TEX19 increased the level of CDK4 protein by influencing SKP2-mediated ubiquitination of CDK4, thereby promoting the progression of breast cancer.

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STUDY QUESTION: What is the functional significance of Tex13b in male germ cell development and differentiation? SUMMARY ANSWER: Tex13b regulates male germ cell differentiation by metabolic reprogramming during spermatogenesis. WHAT IS KNOWN ALREADY: Studies in mice and humans suggest that TEX13B is a transcription factor and is exclusively expressed in germ cells. STUDY DESIGN, SIZE, DURATION: We sequenced the coding regions of TEX13B in 628 infertile men and 427 ethnically matched fertile control men. Further, to identify the molecular function of Tex13b, we created a Tex13b knockout and conditional overexpression system in GC-1spg (hereafter, GC-1) cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our recent exome sequencing study identified novel candidate genes for male infertility. TEX13B was found to be one of the potential candidates, hence we explored the role of TEX13B in male infertility within a large infertile case-control cohort. We performed functional analyses of Tex13b in a GC-1 cell line using CRISPR-Cas9. We differentially labelled the cell proteins by stable isotope labelling of amino acids in cell culture (SILAC) and performed mass spectrometry-based whole-cell proteomics to identify the differential protein regulation in knockout cells compared to wild-type cells. We found that Tex13b knockout leads to downregulation of the OXPHOS complexes and upregulation of glycolysis genes, which was further validated by western blotting. These results were further confirmed by respirometry analysis in Tex13b knockout cells. Further, we also performed a conditional overexpression of TEX13B in GC-1 cells and studied the expression of OXPHOS complex proteins by western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a rare variant, rs775429506 (p.Gly237Glu), exclusively in two non-obstructive-azoospermia (NOA) men, that may genetically predispose these men for infertility. Further, we demonstrated that Tex13b functions in the transcription regulation of OXPHOS complexes. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: We examined the function of Tex13b in GC-1 in vitro by knocking out and conditional overexpression, for understanding the function of Tex13b in germ cells. Unfortunately, this could not be replicated in either an animal model or in patient-derived tissue due to the non-availability of an animal model or patient's testis biopsies. WIDER IMPLICATIONS OF THE FINDINGS: This study identified that Tex13b plays an important role in male germ cell development and differentiation. The findings of this study would be useful for screening infertile males with spermatogenic failure and counselling them before the implementation of assisted reproduction technique(s). STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Council of Scientific and Industrial Research (CSIR) under the network project (BSC0101 and MLP0113) and SERB, the Department of Science and Technology, Government of India (J C Bose Fellowship: JCB/2019/000027). The authors do not have any competing interest.

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BACKGROUND: Very large chest wall resections can lead to acute thoracic insufficiency syndrome due to the interdependence of lung expansion and thoracic volume. Chest wall tumor surgeries often encounter complications, with the size of the chest wall defect being a significant predictor. Several methods for large chest wall reconstruction have been described, aiming to provide stability, prevent flail chest, and ensure airtight closure. However, no single method fulfills all requirements. Composite chest wall reconstruction using titanium plates and Gore-Tex patches has shown the potential to minimize physiologic abnormalities caused by extensive defects. CASE PRESENTATION: A 42-year-old man with myxofibrosarcoma underwent multiple surgeries, chemotherapies, and radiation therapies due to repeated local recurrences. After right arm amputation and resection of the right third to fifth ribs, a local recurrence was detected. A 30 × 40 cm chest wall defect was resected en bloc, and a titanium plate was used for three-dimensional formability, preventing flail chest and volume loss. The Gore-Tex patch was then reconstructed into an arch shape, allowing lateral thoracic mobility. The patient recovered well and did not experience respiratory dysfunction or local recurrence but later succumbed to distant metastasis. CONCLUSIONS: In this case, the combination of a titanium plate and a Gore-Tex patch proved effective for reconstructing massive lateral chest wall defects. The approach provided stability, preserved thoracic volume, and allowed for lateral mobility. While the patient achieved a successful outcome in terms of local recurrence and respiratory function, distant metastasis remained a challenge for myxofibrosarcoma patients, and its impact on long-term prognosis requires further investigation. Nevertheless, the described procedure offers promise for managing extensive chest wall defects.

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PURPOSE: To assess the clinical outcomes of symblepharon release in patients with ocular surface chemical injury using Gore-Tex as a novel treatment option. METHODS: This was a retrospective analysis of 23 eyes of 22 chemical injury patients done during a period of January 2014 to December 2021 at a tertiary eye care centre in South India. All patients underwent symblepharon lysis along with Gore-Tex application over the sclera with minimum 1 year follow up. The patients were assessed for demographic details, visual acuity, intraocular pressure, anterior and posterior segment details, photographic documentation, preoperative diagnosis, previous surgical details in recurrent cases, surgical procedures, final visual acuity, surgical outcomes, and complications. The clinical outcomes were assessed and outcomes were defined as success, partial success, or failure. RESULTS: The median age was 17 years (IQR, 12-39 years). Among them 10 eyes with symblepharon had grade 3 length, 12 eyes grade 3 width and 12 eyes had grade 3 loss of palisades of Vogt. The success was achieved in 52.2% of the patients; partial success in 34.8% and 13.3% had failure. The mean duration of recurrence was 6.75 ± 3.6 months. Failure was noted in young patients with mean age 9.75years and with grade 3c symblepharon. There was no sight threatening complications noted. CONCLUSION: The study showed very good results with Gore-Tex as a novel treatment option for chemical injury patient with symblepharon formation. It can be easily employed to prevent the symblepharon recurrence of various ocular surface disorders.

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CD8+ exhausted T cells (CD8+ Tex) played a vital role in the progression and therapeutic response of cancer. However, few studies have fully clarified the characters of CD8+ Tex related genes in ovarian cancer (OC). The CD8+ Tex related prognostic signature (TRPS) was constructed with integrative machine learning procedure including 10 methods using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 dataset. Several immunotherapy benefits indicators, including Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore (IPS), TMB score and tumor escape score, were used to explore performance of TRPS in predicting immunotherapy benefits of OC. The TRPS constructed by Enet (alpha = 0.3) method acted as an independent risk factor for OC and showed stable and powerful performance in predicting clinical outcome of patients. The C-index of the TRPS was higher than that of tumor grade, clinical stage, and many developed signatures. Low TRPS score indicated a higher level of CD8+ T cell, B cell, macrophage M1, and NK cells, representing a relative immunoactivated ecosystem in OC. OC patients with low risk score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, suggesting a better immunotherapy response. Moreover, higher TRPS score indicated a higher score of cancer-related hallmarks, including angiogenesis, EMT, hypoxia, glycolysis, and notch signaling. Vitro experiment showed that ARL6IP5 was downregulated in OC tissues and inhibited tumor cell proliferation. The current study constructed a novel TRPS for OC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy benefits for OC patients.

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BACKGROUND: Infertility affects around 15% of all couples worldwide and is increasingly linked to variants in genes specifically expressed in the testis. Well-established causes of male infertility include pathogenic variants in the genes TEX11, TEX14, and TEX15, while few studies have recently reported variants in TEX13B, TEX13C, FAM9A (TEX39A), and FAM9B (TEX39B). OBJECTIVES: We aimed at screening for novel potential candidate genes among the human TEX ("testis expressed") genes as well as verifying previously described disease associations in this set of genes. MATERIALS AND METHODS: To this end, we screened the exome sequencing data of 1305 men, including 1056 crypto- and azoospermic individuals, and determined cell-specific expression by analyzing testis-specific single-cell RNA sequencing data for genes with identified variants. To investigate the overarching role in male fertility, we generated testis-specific knockdown (KD) models of all 10 orthologous TEX genes in Drosophila melanogaster. RESULTS: We detected rare potential disease-causing variants in TEX10, TEX13A, TEX13B, TEX13C, TEX13D, ZFAND3 (TEX27), TEX33, FAM9A (TEX39A), and FAM9B (TEX39B), in 28 infertile men, of which 15 men carried variants in TEX10, TEX27, and TEX33. The KD of TEX2, TEX9, TEX10, TEX13, ZFAND3 (TEX27), TEX28, TEX30, NFX1 (TEX42), TEX261, and UTP4 (TEX292) in Drosophila resulted in normal fertility. DISCUSSION: Based on our findings, the autosomal dominant predicted genes TEX10 and ZFAND3 (TEX27) and the autosomal recessive predicted gene TEX33, which all three are conceivably required for germ cell maturation, were identified as novel potential candidate genes for human non-obstructive azoospermia. We additionally identified hemizygous loss-of-function (LoF) variants in TEX13B, TEX13C, and FAM9A (TEX39A) as unlikely monogenic culprits of male infertility as LoF variants were also found in control men. CONCLUSION: Our findings concerning the X-linked genes TEX13B, TEX13C, and FAM9A (TEX39A) contradict previous reports and will decrease false-positive reports in genetic diagnostics of azoospermic men.

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Rewiring exhausted CD8+ T (Tex) cells toward functional states remains a therapeutic challenge. Tex cells are epigenetically programmed by the transcription factor Tox. However, epigenetic remodeling occurs as Tex cells transition from progenitor (Texprog) to intermediate (Texint) and terminal (Texterm) subsets, suggesting development flexibility. We examined epigenetic transitions between Tex cell subsets and revealed a reciprocally antagonistic circuit between Stat5a and Tox. Stat5 directed Texint cell formation and re-instigated partial effector biology during this Texprog-to-Texint cell transition. Constitutive Stat5a activity antagonized Tox and rewired CD8+ T cells from exhaustion to a durable effector and/or natural killer (NK)-like state with superior anti-tumor potential. Temporal induction of Stat5 activity in Tex cells using an orthogonal IL-2:IL2Rß-pair fostered Texint cell accumulation, particularly upon PD-L1 blockade. Re-engaging Stat5 also partially reprogrammed the epigenetic landscape of exhaustion and restored polyfunctionality. These data highlight therapeutic opportunities of manipulating the IL-2-Stat5 axis to rewire Tex cells toward more durably protective states.

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The link between T-cell exhaustion (TEX) and PAFAH1B3 in hepatocellular carcinoma (HCC) remains unknown, even though both of them are related to overall survival. PAFAH1B3 expression was investigated in TCGA and ICGC data, and 50 paired clinical tissue section samples were used for qRT-PCR and immunohistochemistry (IHC) confirmation. The Immunocell Abundance Identifier (ImmuCellAI) was used to precisely calculate the abundance of TEX, and its accuracy was verified by single-cell RNA-seq and labeling of CD8 + T cells in clinical tissue sections. The IMVigor 210 cohort was used to demonstrate the predictive value of PAFAH1B3 for immunotherapy efficacy. Increased PAFAH1B3 is a standalone effector of poor prognosis in HCC patients. Patients who had greater PAFAH1B3 levels had more TEX infiltration. PAFAH1B3 expression was increased in TEX in the single-cell RNA-seq data. Patients with high PAFAH1B3 expression were more likely to respond favorably to PD1/PD-L1 treatment. In conclusion, PAFAH1B3 is closely related to TEX in the tumor microenvironment (TME) and can be a useful indicator for PD1/PD-L1 therapy.

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BACKGROUND: Patch repair of congenital diaphragmatic hernia (CDH) using Gore-Tex® is associated with infection, adhesions, hernia recurrence, long-term musculoskeletal sequels and poor tissue regeneration. To overcome these limitations, the performance of two novel biodegradable membranes was tested to repair CDH in a growing pig model. METHODS: Twelve male pigs were randomly assigned to 3 different groups of 4 animals each, determined by the type of patch used during thoracoscopic diaphragmatic hernia repair (Gore-Tex®, polycaprolactone electrospun membrane-PCLem, and decellularized human chorion membrane-dHCM). After 7 weeks, all animals were euthanized, followed by necropsy for diaphragmatic evaluation and histological analysis. RESULTS: Thoracoscopic defect creation and diaphragmatic repair were performed without any technical difficulty in all groups. However, hernia recurrence rate was 0% in Gore-Tex®, 50% in PCLem and 100% in dHCM groups. At euthanasia, Gore-Tex® patches appeared virtually unchanged and covered with a fibrotic capsule, while PCLem and dHCM patches were replaced by either floppy connective tissue or vascularized and floppy regenerated membranous tissue, respectively. CONCLUSION: Gore-Tex® was associated with a higher survival rate and lower recurrence. Nevertheless, the proposed biodegradable membranes were associated with better tissue integration when compared with Gore-Tex®.

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Testis expression 10 (Tex10) is reported to be associated with tumorigenesis in several types of cancer types, but its role in hepatocellular carcinoma (HCC) metastasis has not been investigated. In this study, the expression of Tex10 in the HCC cell line and tissue microarray was determined by Western blot and immunohistochemistry (IHC), respectively. RNA sequencing-based transcriptome analysis was performed to identify the Tex10-mediated biological process. Cell Counting Kit-8, colony formation, transwell assays, xenograft tumor growth, and lung metastasis experiments in nude mice were applied to assess the effects of Tex10 on cell proliferation, migration, invasion, and metastasis. The underlying mechanisms were further investigated using dual-luciferase reporter, co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. We found that Tex10 was upregulated in HCC tumor tissues compared to adjacent normal tissues, with its expression correlated with a poor prognosis. Gene ontology function enrichment analysis revealed alterations in several biological processes in response to Tex10 knockdown, especially cell motility and cell migration. Functional studies demonstrated that Tex10 promotes HCC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Moreover, Tex10 was shown to regulate invasion and epithelial-mesenchymal transition via signal transducer and activator of transcription 3 (STAT3) signaling. Mechanistically, Tex10 was found to interact with STAT3 and promote its transcriptional activity. In addition, we found that Tex10 promotes p300-mediated STAT3 acetylation, while p300 silencing abolishes Tex10-enhanced STAT3 transcriptional activity. Together, these findings indicate that Tex10 functions as an oncogene by upregulating STAT3 activity, thus suggesting that Tex10 may serve as a prognostic biomarker and/or therapeutic target for HCC patients.

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Nitrososphaeria in the phylum Crenarchaeota, is a widespread archaeal class in the oceanic realm, playing an important role in the marine carbon and nitrogen cycle. Nitrososphaeria-derived membrane lipids, i.e., isoprenoid glycerol dialkyl glycerol tetraethers (GDGTs), are commonly employed to reconstruct past water temperatures using the TetraEther indeX of 86 carbon atoms (TEX86). This index is of particular importance for the brackish Baltic Sea as to date it appears to be the only applicable organic temperature proxy. In this study, we investigated the distribution of intact and core GDGTs and their potential source organisms in the water column of three deep basins located in the central Baltic Sea to evaluate the application of TEX86. A lipidomic approach on suspended particulate matter was combined with the molecular techniques 16S rRNA gene amplicon sequencing and CARD-FISH. The archaeal community was dominated by Nitrosopumilus (~83-100% of the total archaeal sequences). As other detected taxa known to produce GDGTs each represented less than 2% of the total archaeal sequences, Nitrosopumilus is likely the most dominant GDGT producer in the central Baltic Sea. However, the occurrence of phosphohexose (PH), instead of hexose-phosphohexose (HPH) headgroups, suggested that Nitrosopumilus in the Baltic Sea may differ physiologically from representatives of marine settings and other marginal seas, such as the Black Sea. In the Baltic Sea, Nitrosopumilus is most abundant in the suboxic zone, where intact cells peak according to both CARD-FISH data and intact polar lipid concentrations. The presented data therefore suggest that TEX86 reflects subsurface rather than surface temperature in the central Baltic Sea.