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The deep ocean releases large amounts of old, pre-industrial carbon dioxide (CO2) to the atmosphere through upwelling in the Southern Ocean, which counters the marine carbon uptake occurring elsewhere. This Southern Ocean CO2 release is relevant to the global climate because its changes could alter atmospheric CO2 levels on long time scales, and also affects the present-day potential of the Southern Ocean to take up anthropogenic CO2. Here, year-round profiling float measurements show that this CO2 release arises from a zonal band of upwelling waters between the Subantarctic Front and wintertime sea-ice edge. This band of high CO2 subsurface water coincides with the outcropping of the 27.8 kg m-3 isoneutral density surface that characterizes Indo-Pacific Deep Water (IPDW). It has a potential partial pressure of CO2 exceeding current atmospheric CO2 levels (∆PCO2) by 175 ± 32 μatm. Ship-based measurements reveal that IPDW exhibits a distinct ∆PCO2 maximum in the ocean, which is set by remineralization of organic carbon and originates from the northern Pacific and Indian Ocean basins. Below this IPDW layer, the carbon content increases downwards, whereas ∆PCO2 decreases. Most of this vertical ∆PCO2 decline results from decreasing temperatures and increasing alkalinity due to an increased fraction of calcium carbonate dissolution. These two factors limit the CO2 outgassing from the high-carbon content deep waters on more southerly surface outcrops. Our results imply that the response of Southern Ocean CO2 fluxes to possible future changes in upwelling are sensitive to the subsurface carbon chemistry set by the vertical remineralization and dissolution profiles.

Pancreatic neuroendocrine tumor (pNET) is the second most common malignant tumors of the pancreas. Multiple endocrine neoplasia 1 ( MEN1) is the most frequently mutated gene in pNETs and MEN1-encoded protein, menin, is a scaffold protein that interacts with transcription factors and chromatin-modifying proteins to regulate various signaling pathways. However, the role of MEN1 in lipid metabolism has not been studied in pNETs. In this study, we perform targeted metabolomics analysis and find that MEN1 promotes the generation and oxidation of polyunsaturated fat acids (PUFAs). Meanwhile lipid peroxidation is a hallmark of ferroptosis, and we confirm that MEN1 promotes ferroptosis by inhibiting the activation of mTOR signaling which is the central hub of metabolism. We show that stearoyl-coA desaturase (SCD1) is the downstream of MEN1-mTOR signaling and oleic acid (OA), a metabolite of SCD1, recues the lipid peroxidation caused by MEN1 overexpression. The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, we find that BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pNETs that targets mTOR signaling. In addition, combined use everolimus with ferroptosis inducer, RSL3, possesses a more powerful ability to kill cells, which may provide a new strategy for the comprehensive therapy of pNETs.

Neuropeptide Y (NPY), a 36‐amino‐acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]–NPY and [Leu31, Pro34]–NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N‐terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor‐selective drug development. In this study, we report three cryo‐electron microscopy (cryo‐EM) structures of Gi2‐coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]–NPY. Combined with cell‐based assays, our study not only reveals the conserved peptide‐binding mode of NPY receptors but also identifies an additional sub‐pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub‐pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family. [ABSTRACT FROM AUTHOR]

Background: The incidence of postoperative pancreatic fistula (POPF) following enucleation is high, and prophylactic pancreaticojejunostomy (PPJ) is frequently performed. Minimally invasive enucleation (MEN) has been demonstrated to be safe and feasible, leaving most enucleation wounds exposed. Methods: The clinical data of 40 patients who underwent open enucleation with PPJ at our center between 2012 and 2021 were compared with those of 80 patients who underwent MEN. Results: The MEN group had better outcomes than the PPJ group in terms of intraoperative bleeding (50.0 versus 100.0 mL), postoperative semi‐liquid diet recovery (2.0 versus 5.0 days), and postoperative length of stay (7.7 versus 12.5 days). While the MEN group had higher rates of complex enucleation (60.0% versus 40.0%), main pancreatic duct repair (32.5% versus 10.0%), discharge with drains (48.8% versus 25.0%), and grade B POPFs (47.5% versus 17.5%). Both surgical methods effectively preserved pancreatic function; however, two patients in the PPJ group experienced severe haemorrhaging and died. Additionally, during the follow‐up period, gastrointestinal bleeding was found and discomfort in the surgical area was reported. Conclusion: Pancreatic enucleation combined with PPJ should be avoided, and although a biochemical or grade B POPF may develop after MEN, it can be compensated for by preserving pancreatic function and ensuring a good long‐term quality of life in the patients. [ABSTRACT FROM AUTHOR]

• Human Alu-INSL3 might be on its way to functionality and has potential to antagonize LGR8-INSL3 function. • Provide an example of the evolutionary trajectory of a variant peptide hormone antagonist that caused by the insertion of an Alu element in primates. • A new exon in the INSL3 gene, which evolved ~50 million years ago, and led to a splicing variant of INSL3 gene. Alu sequences are the most abundant repetitive elements in the human genome, and have proliferated to more than one million copies in the human genome. Primate-specific Alu sequences account for ~10% of the human genome, and their spread within the genome has the potential to generate new exons. The new exons produced by Alu elements appear in various primate genes, and their functions have been elucidated. Here, we identified a new exon in the insulin-like 3 gene (INSL3), which evolved ~50 million years ago, and led to a splicing variant with 31 extra amino acid residues in addition to the original 95 nucleotides (NTs) of INSL3. The Alu-INSL3 isoform underwent diverse changes during primate evolution; we identified that human Alu-INSL3 might be on its way to functionality and has potential to antagonize LGR8-INSL3 function. Therefore, the present study is designed to provide an example of the evolutionary trajectory of a variant peptide hormone antagonist that caused by the insertion of an Alu element in primates. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the expression and function of WNT16, a member of the WNT family protein, in the context of systemic lupus erythematosus (SLE)., Methods: WNT16 expression was assessed in peripheral blood mononuclear cells (PBMCs) from 35 SLE patients and 25 healthy individuals using quantitative polymerase chain reaction. Additionally, serum WNT16 protein levels were quantified via enzyme-linked immunosorbent assay in 162 SLE patients, 96 healthy controls (HC), and disease controls comprised 154 individuals with rheumatoid arthritis (RA) and Sjögren's syndrome (SS). We investigated the associations between WNT16 protein levels and clinical manifestations, laboratory indices, and disease activity in SLE patients. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of serum WNT16 for SLE. Furthermore, we performed a knockdown assay on Jeko-1 cells and assessed cell proliferation and apoptosis using Cell Counting Kit-8 and flow cytometry., Results: WNT16 mRNA in SLE patients' PBMCs were significantly lower than those in HC. Furthermore, serum WNT16 in SLE patients were markedly reduced compared to HC, RA, and SS cohorts. ROC curve analysis indicated that plasma WNT16 levels could serve as a potential biomarker for SLE identification (AUC=0.809, SLE vs. HC; AUC=0.760, SLE vs. RA; AUC=0.710, SLE vs. SS). Notably, a weak positive correlation was observed between WNT16 protein and both alkaline phosphatase and lymphocyte percentages. Conversely, a weak negative correlation existed between WNT16 and low-density lipoprotein, neutrophil percentage, and the incidence of pleurisy and disease activity. Additionally, our study confirmed that WNT16 knockdown impairs cell proliferation and enhances apoptosis., Conclusions: Serum WNT16 levels effectively differentiate SLE patients from healthy controls and individuals with other autoimmune disorders. WNT16 serves as a potential biomarker with high sensitivity. The diminished expression of WNT16 in SLE may have a significant role in its pathogenesis through the regulation of cell proliferation and apoptosis.

Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro 34 ]-NPY and [Leu 31 , Pro 34 ]-NPY, mainly acting on Y 1 R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y 2 R. However, the recognition mechanisms of Y 1 R and Y 2 R with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled Y 1 R and Y 2 R in complexes with NPY, as well as Y 1 R bound to a selective agonist [Leu 31 , Pro 34 ]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of Y 1 R evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family., Competing Interests: The authors declare no competing interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Objective: To compare the effectiveness of complex defects repair between using chimeric anterolateral thigh flap and series-wound flaps after resection of oral and maxillofacial cancer., Methods: After resection of oral and maxillofacial cancer, defect was repaired with chimeric anterolateral thigh flap in 39 patients between January 2011 and July 2014 (chimeric anterolateral thigh flap group); and defect was repaired with series-wound flaps in 35 patients between January 2009 and December 2010 (series-wound flaps group). There was no significant difference in gender, age, duration of disease, tumor type, tumor staging, defect location, and defect area between 2 groups (P > 0.05). The operation time, flap harvesting and microvascular anastomosis time, stomach tube extraction time, and oral feeding time were recorded and compared between 2 groups, and postoperative complications were observed; the effectiveness was evaluated according to clinical efficacy evaluation table of bone and soft tissue defects reconstruction surgery in oral and maxillofacial region., Results: Vascular crisis occurred in 2 cases of chimeric anterolateral thigh flap group, and 4 cases of series-wound flaps group. Partial necrosis appeared at distal end of a series-wound flaps, and oral fistula and infection developed in 3 series-wound flaps. The other flaps and the grafted skin at donor site survived; wounds at recipient site healed by first intention. The operation time, stomach tube extraction time, and oral feeding time of chimeric anterolateral thigh flap group were significantly shorter than those of series-wound flaps group (P < 0.05), while the flap harvesting and microvascular anastomosis time was significantly longer than that of series-wound flaps group (P < 0.05). The patients were followed up 1-5 years (mean, 2.5 years). At 3 months after operation, the appearance, patients' satisfaction, working conditions, oral closure function, chew, language performance, and swallowing scores of the chimeric anterolateral thigh-flap group were significantly better than those of the series-wound flaps group (P < 0.05), while there was no significant difference in diet, mouth opening degree, oral cavity holding water test, and occlusion scores between the 2 groups (P > 0.05)., Conclusion: Using chimeric anterolateral thigh flap for defect repair after resection of oral and maxillofacial cancer can significantly shorten the operation time, accelerate postoperative rehabilitation, and help the functional recovery of oral closure, chewing, language performance, swallowing function when compared with the series-wound flaps.