Notes

Parallel uniportal video-assisted thoracic surgical treatment regarding pulmonary acne nodules and synchronous mediastinal skin lesions.
While many studies have evaluated the relationship between BMI and breast cancer outcomes, it is unclear whether this relationship is consistent between early breast cancer (BC) and advanced BC. The study included 5099 patients with HER2 positive early BC (EBC) and 3496 with HER2 positive advanced BC (ABC). In the EBC cohort, higher BMI was associated with worse overall survival (OS) (HR [95% CI] overweight = 1.30 [1.13-1.51]; obese = 1.37 [1.14-1.64], P =  less then  0.001), and worse disease-free survival (overweight = 1.10 [0.98-1.24]; obese = 1.20 [1.04-1.39], P = 0.061). In contrast, for the ABC cohort, higher BMI was significantly associated with improved OS (overweight = 0.85 [0.76-0.96]; obese = 0.82 [0.72-0.95], P = 0.014), and progression-free survival (overweight = 0.91 [0.83-1.01]; obese = 0.87 [0.77-0.98], P = 0.034). In this large high-quality dataset, higher BMI was independently associated with worse survival in EBC, paradoxically in ABC higher BMI was independently associated with improved survival.Dynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington's disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.Mitochondria-lysosome contacts are recently identified sites for mediating crosstalk between both organelles, but their role in normal and diseased human neurons remains unknown. In this study, we demonstrate that mitochondria-lysosome contacts can dynamically form in the soma, axons, and dendrites of human neurons, allowing for their bidirectional crosstalk. Parkinson's disease patient derived neurons harboring mutant GBA1 exhibited prolonged mitochondria-lysosome contacts due to defective modulation of the untethering protein TBC1D15, which mediates Rab7 GTP hydrolysis for contact untethering. This dysregulation was due to decreased GBA1 (β-glucocerebrosidase (GCase)) lysosomal enzyme activity in patient derived neurons, and could be rescued by increasing enzyme activity with a GCase modulator. These defects resulted in disrupted mitochondrial distribution and function, and could be further rescued by TBC1D15 in Parkinson's patient derived GBA1-linked neurons. Together, our work demonstrates a potential role of mitochondria-lysosome contacts as an upstream regulator of mitochondrial function and dynamics in midbrain dopaminergic neurons in GBA1-linked Parkinson's disease.Malignant T-cell-amplified sequence 1 (Mct-1) has been reported as an oncogene in multiple malignant diseases. However, the function of Mct-1 in hepatocellular carcinoma (HCC) and the molecular mechanisms underlying tumor progression have not been explored. In this study, Mct-1 expression levels in HCC tissues and cells were detected by quantitative real-time PCR and western blotting. Mct-1 shRNAs and overexpression vector were transfected into HCC cells to downregulate or upregulate Mct-1 expression. In vitro and in vivo assays were performed to investigate the function of Mct-1 in cell proliferation and apoptosis. RNA sequencing analysis (RNA-seq) was performed to explore differences in gene expression when silenced Mct-1 expression. Mct-1 was upregulated in HCC specimens and cell lines, and higher expression of Mct-1 was predictive of poor survival. Overexpression of Mct-1 was shown to promote cell proliferation and repress cell apoptosis both in vitro and in vivo. The results of RNA-seq indicated that knockdown of Mct-1 suppressed Yap expression, while the results of the luciferase assay also revealed that Mct-1 increases the activity of the Yap promoter. Restoration of Yap expression in Mct-1 knockdown cells partially recovered the promotion of cell proliferation and inhibition of apoptosis. Collectively, these results indicate that Mct-1 acts as a tumor promoter gene in HCC progression by up-regulating Yap expression and, thus, could serve a novel potential diagnostic and prognostic biomarker for HCC.X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Polyinosinic acid-polycytidylic acid in vivo Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
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