Mouse totipotent stem cells captured and maintained through spliceosomal repression.

Since establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable with in vivo blastomeres with embryonic and extraembryonic developmental potential has been a challenge. Here we report that spliceosomal repression in mouse ESCs drives a pluripotent-to-totipotent state transition. Using the splicing inhibitor pladienolide B, we achieve stable in vitro culture of totipotent ESCs comparable at molecular levels with 2- and 4-cell blastomeres, which we call totipotent blastomere-like cells (TBLCs). Mouse chimeric assays combined with single-cell RNA sequencing (scRNA-seq) demonstrate that TBLCs have a robust bidirectional developmental capability to generate multiple embryonic and extraembryonic cell lineages. Mechanically, spliceosomal repression causes widespread splicing inhibition of pluripotent genes, whereas totipotent genes, which contain few short introns, are efficiently spliced and transcriptionally activated. Our study provides a means for capturing and maintaining totipotent stem cells.

JMJD6 Licenses ERα-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex.

Whereas the actions of enhancers in gene transcriptional regulation are well established, roles of JmjC-domain-containing proteins in mediating enhancer activation remain poorly understood. Here, we report that recruitment of the JmjC-domain-containing protein 6 (JMJD6) to estrogen receptor alpha (ERα)-bound active enhancers is required for RNA polymerase II recruitment and enhancer RNA production on enhancers, resulting in transcriptional pause release of cognate estrogen target genes. JMJD6 is found to interact with MED12 in the mediator complex to regulate its recruitment. Unexpectedly, JMJD6 is necessary for MED12 to interact with CARM1, which methylates MED12 at multiple arginine sites and regulates its chromatin binding. Consistent with its role in transcriptional activation, JMJD6 is required for estrogen/ERα-induced breast cancer cell growth and tumorigenesis. Our data have uncovered a critical regulator of estrogen/ERα-induced enhancer coding gene activation and breast cancer cell potency, providing a potential therapeutic target of ER-positive breast cancers.

CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development.

Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.

Protective effects of COVID-19 vaccination in splenectomized patients with immune thrombocytopenia.

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.

Artificial intelligence automated surgical phases recognition in intraoperative videos of laparoscopic pancreatoduodenectomy.

BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is one of the most challenging operations and has a long learning curve. Artificial intelligence (AI) automated surgical phase recognition in intraoperative videos has many potential applications in surgical education, helping shorten the learning curve, but no study has made this breakthrough in LPD. Herein, we aimed to build AI models to recognize the surgical phase in LPD and explore the performance characteristics of AI models. METHODS: Among 69 LPD videos from a single surgical team, we used 42 in the building group to establish the models and used the remaining 27 videos in the analysis group to assess the models' performance characteristics. We annotated 13 surgical phases of LPD, including 4 key phases and 9 necessary phases. Two minimal invasive pancreatic surgeons annotated all the videos. We built two AI models for the key phase and necessary phase recognition, based on convolutional neural networks. The overall performance of the AI models was determined mainly by mean average precision (mAP). RESULTS: Overall mAPs of the AI models in the test set of the building group were 89.7% and 84.7% for key phases and necessary phases, respectively. In the 27-video analysis group, overall mAPs were 86.8% and 71.2%, with maximum mAPs of 98.1% and 93.9%. We found commonalities between the error of model recognition and the differences of surgeon annotation, and the AI model exhibited bad performance in cases with anatomic variation or lesion involvement with adjacent organs. CONCLUSIONS: AI automated surgical phase recognition can be achieved in LPD, with outstanding performance in selective cases. This breakthrough may be the first step toward AI- and video-based surgical education in more complex surgeries.

Textbook oncologic outcomes are associated with increased overall survival in patients with pancreatic head cancer after undergoing laparoscopic pancreaticoduodenectomy.

BACKGROUND: Textbook oncologic outcomes (TOO) have been used to evaluate long-term oncologic outcomes for patients after pancreaticoduodenectomy (PD) but not laparoscopic pancreaticoduodenectomy (LPD). The aim of the study was to assess the prognostic value of TOO for patients with pancreatic head cancer undergoing LPD and discuss the risk factors associated with achieving TOO. METHODS: Patients with pancreatic head cancer who underwent LPD in West China Hospital from January 2015 to May 2022 were consecutively enrolled. TOO was defined as achieving R0 resection, examination of ≥ 12 lymph nodes, no prolonged length of stay, no 30-day readmission/death, and receiving adjuvant chemotherapy. Survival analysis was used to determine the prognostic value of a TOO on overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify the risk factors of a TOO. The rates of a TOO and of each indicator were compared in patients who suffered or not from delayed gastric emptying (DGE). RESULTS: A total of 44 (25.73%) patients achieved TOO which was associated with improved median OS (TOO 32 months vs. non-TOO 20 months, P = 0.034) and a better RFS (TOO 19 months vs. non-TOO 13 months, P = 0.053). Patients suffering from DGE [odds ratio (OR) 4.045, 95% CI 1.151-14.214, P = 0.029] were independent risk factors for TOO. In addition, patients with DGE after surgery had a significantly lower rate of TOO (P = 0.015) than patients without DGE. CONCLUSIONS: As there were significant differences between patients who achieved TOO or not, TOO is a good indicator for long-term oncologic outcomes in patients with pancreatic head cancer after undergoing LPD. DGE is the risk factor for achieving TOO, so it is important to prevent the DGE after LPD to improve the rate of TOO.

Delayed gastric emptying after laparoscopic pancreaticoduodenectomy: a single-center experience of 827 cases.

BACKGROUND: Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. METHODS: This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. RESULTS: A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p < 0.001) were independent significant risk factors for DGE. Seventy-six (53.5%) patients were diagnosed with primary DGE, whereas 66 (46.5%) patients had DGE secondary to concomitant complications. Higher body mass index, soft pancreatic texture, and perioperative transfusion were independent risk factors for secondary DGE. Hospital stay and drainage tube removal time were significantly longer in the DGE and secondary DGE groups. CONCLUSION: Identifying patients at an increased risk of DGE and secondary DGE can be used to intervene earlier, avoid potential risk factors, and make more informed clinical decisions to shorten the duration of perioperative management.

Quercetin inhibits the metabolism of arachidonic acid by inhibiting the activity of CYP3A4, thereby inhibiting the progression of breast cancer.

BACKGROUND: Recent years have witnessed impressive growth in applying natural medicine in tumor treatment. Saffron is reported to elicit an inhibitory property against BC. Herein, we sought to explore the specific components and mechanistic basis of saffron's anti-breast carcinoma (BC) function. METHODS: Bioinformatics analysis was employed to analyze saffron components' anti-BC activity and screen the corresponding target genes involved in BC. Then, the roles of the main saffron ingredient quercetin in the activity of BC cells were examined using CCK-8, MTS, flow cytometry, colony formation, Transwell, and Gelatin zymogram assays. Additionally, the interactions among Quercetin, EET, and Stat3 were assessed by immunofluorescence and Western blot, and LC-MS/MS determined the levels of AA, EETs, and CYP3A. Finally, BC xenograft mouse models were established to verify the anti-BC function of Quercetin in vivo. RESULTS: Quercetin, the main active component of saffron, inhibited BC progression. Quercetin suppressed BC cell growth, migration, and invasion and inhibited CYP3A4 expression and activity in BC. Mechanistically, Quercetin down-regulated CYP3A4 to block the nuclear translocation of Stat3 by decreasing the metabolization of AA to EETs, thereby alleviating BC. Moreover, exogenously added EETs counteracted the anti-tumor effect of Quercetin on BC. Quercetin also inhibited the tumor growth of tumor-bearing nude mice. CONCLUSION: Quercetin could inhibit the activity of CYP3A to down-regulate AA metabolites EETs, consequently hampering p-Stat3 and nuclear translocation, thus impeding BC development.

Laparoscopic Transduodenal Ampullectomy: How We Have Standardized the Technique (with Video).

BACKGROUND: The procedure of choice for the resection of ampullary tumors comprises transduodenal ampullectomy (TDA), endoscopic papillectomy (EP), and pancreaticoduodenectomy (PD).1 For neoplasms with low-grade dysplasia, TDA and EP have equivalent efficacies and lower morbidities than PD1. Compared with EP, also as an organ-preserving procedure, TDA could be applicable for tumors involving the pancreatic ducts or common bile ducts.2 Because TDA has a lower incidence of postoperative gastrointestinal bleeding and a higher R0 resection rate, its use could avoid the need to use multiple endoscopic procedures for larger lesions.3 Furthermore, during TDA, surgeons could convert to PD as necessary. However, TDA has rarely been performed using a minimally invasive approach that addresses the shortcomings of both the endoscopic and open surgical techniques without adding significant morbidity or compromising outcomes.2,4 Conventional laparoscopic TDA (LTDA) remains limited due to the complexity of the surgical anatomy of the ampulla and the reconstruction required compared with robot-assisted procedures.2-5 However, robot-assisted surgery is less popular and much more expensive than laparoscopic surgery. This report with a video describes the LTDA approach to standardize and simplify the surgical processes. METHODS: A 48-year-old man was admitted to the hospital with epigastric pain. He had a history of cholecystolithiasis with chronic cholecystitis. A tumor approximately 2.2 cm in diameter located in the duodenal papilla was diagnosed by an enhanced computed tomography (CT) scan. The endoscopic biopsy result indicated a villous adenoma with moderate dysplasia. Laparoscopic TDA and cholecystectomy were planned. However, if the frozen sample analysis showed adenocarcinoma, laparoscopic PD (LPD) would be applied. The patient was placed in the supine position with both legs apart. Trocars were distributed in the same manner as in the authors' previous study to facilitate conversion to LPD.6 The procedure began with kocherization and dissection of the gastrocolic ligament to explore the second and third portions of the duodenum. A figure-eight suture was made using 4-0 prolene in the seromuscular layer, and then the duodenum was retracted to the left side of the patient. A longitudinal duodenotomy was made, and the ampulla of Vater was identified. A transfixing suture was placed through the tumor. Submucosal injection of norepinephrine (1:500) was performed to divide the mucosa from the muscular planes. Ampullectomy was performed by first dissecting in the submucosal plane with a harmonic scalpel at the 6 o'clock position until the pancreatic duct was reached. A 6-Fr plastic catheter was inserted into the pancreatic duct for subsequent reconstruction. Continued dissection around the tumor identified the bile duct. Another 6-Fr plastic catheter was inserted into the bile duct. The dissection was completed in the submucosal plane, and the specimen was retrieved for frozen sectioning. After confirmation of villous adenoma with moderate dysplasia and the proximal margin without residual tumor on frozen biopsy, reconstruction was performed. The septum between the ducts was plastered, and the bile and pancreatic ducts were reconstructed on the duodenal wall with 5-0 PDS-II interrupted sutures to ensure that these ducts remained patent and connected. After reconstruction, the plastic catheter was kept in the pancreatic duct but removed from the bile duct. Then, cholecystectomy was applied. Finally, the duodenum was closed obliquely in two layers, and two drains were routinely placed. RESULTS: The operation time was 139 min, and the estimated blood loss was 50 ml. Final pathology confirmed villous adenoma with mild to moderate dysplasia. The postoperative course was uneventful, with a hospital stay of 9 days. There was no evidence of recurrence or patency of the reimplanted ducts 5 months after surgery. From February 2022 to May 2022, four cases of LTDA with the same surgical processes were managed by the authors, and all the patients recovered quickly without any postoperative complications. CONCLUSION: After standardization of the surgical processes, laparoscopic TDA was safe for highly selected patients. However, long-term follow-up is required to observe the quality of life and survival of patients.

ANXA7 Regulates Platelet Lipid Metabolism and Ca2+ Release in Arterial Thrombosis.

[Figure: see text].

Microsomal prostaglandin E synthase-1 inhibition promotes shunting in arachidonic acid metabolism during inflammatory responses in vitro.

Microsomal Prostaglandin E Synthase 1 (mPGES-1) is the key enzyme for the generation of the pro-inflammatory lipid mediator prostaglandin E2 (PGE2), which contributes to several pathological features of many diseases. Inhibition of mPGES-1 has been shown to be a safe and effective therapeutic strategy in various pre-clinical studies. In addition to reduced PGE2 formation, it is also suggested that the potential shunting into other protective and pro-resolving prostanoids may play an important role in resolution of inflammation. In the present study, we analysed the eicosanoid profiles in four in vitro inflammation models and compared the effects of mPGES-1 inhibition with those of cyclooxygenase-2 (Cox-2) inhibition. Our results showed a marked shift to the PGD2 pathway under mPGES-1 inhibition in A549 cells, RAW264.7 cells and mouse bone marrow-derived macrophages (BMDMs), whereas enhanced prostacyclin production was observed in rheumatoid arthritis synovial fibroblasts (RASFs) treated with an mPGES-1 inhibitor. As expected, Cox-2 inhibition completely suppressed all prostanoids. This study suggests that the therapeutic effects of mPGES-1 inhibition may be mediated by modulation of other prostanoids in addition to PGE2 reduction.

Single-port laparoscopic pancreaticoduodenectomy.

BACKGROUND: Performing a single-port laparoscopic pancreatectomy is technically challenging. Single-port laparoscopic pancreaticoduodenectomy (SPLPD) is rarely reported in English literature. METHODS: Eighty-seven cases of laparoscopic pancreaticoduodenectomy (LPD) were performed by a single surgical team in the Department of Pancreatic Surgery, West China Hospital, Sichuan University between February 2020 and December 2020. Among these, 13 cases of LPD (group 1) were performed using a single-port device. Basing on the same inclusion and exclusion criteria, 68 cases of LPD performed using traditional 5-trocar were included as a control group (group 2). The patient's demographic characteristics, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. RESULTS: Five men and eight women were included in the SPLPD group. The median age of these patients was 57 years. The patients who underwent SPLPD required a longer operative time (332.7 ± 38.1 min vs. 305.8 ± 64.7 min; p = 0.03) than those in the LPD group. The estimated blood loss, conversion rate, blood transfusion rate, time to oral intake, postoperative hospital stays, and perioperative complications were comparable between the two groups. The short-term oncological outcomes, such as R0 rate and lymph node harvested, were comparable between the two groups. The 90-day mortality of all patients was zero. CONCLUSIONS: SPLPD is a safe and feasible procedure for well-selected patients in an experienced minimally invasive pancreatic surgery team. SPLPD may provide several potential advantages, such as the requirement of fewer trocars, fewer abdominal complications, and reduced participation of assistants than conventional LPD.

The short- and long-term outcomes of laparoscopic pancreaticoduodenectomy combining with different type of mesentericoportal vein resection and reconstruction for pancreatic head adenocarcinoma: a Chinese multicenter retrospective cohort study.

BACKGROUND: The results of laparoscopic pancreaticoduodenectomy combining with mesentericoportal vein resection and reconstruction (LPD-MPVRs) for pancreatic head adenocarcinoma are rarely reported. The aim of present study was to explore the short- and long-term outcomes of different type of LPD-MPVRs. METHODS: Patients who underwent LPD-MPVRs in 14 Chinese high-volume pancreatic centers between June 2014 and December 2020 were selected and compared. RESULTS: In total, 142 patients were included and were divided into primary closure (n = 56), end-end anastomosis (n = 43), or interposition graft (n = 43). Median overall survival (OS) and median progress-free survival (PFS) between primary closure and end-end anastomosis had no difference (both P > 0.05). As compared to primary closure and end-end anastomosis, interposition graft had the worst median OS (12 months versus 19 months versus 17 months, P = 0.001) and the worst median PFS (6 months versus 15 months versus 12 months, P < 0.000). As compared to primary closure, interposition graft had almost double risk in major morbidity (16.3 percent versus 8.9 percent) and about triple risk (10 percent versus 3.6 percent) in 90-day mortality, while End-end anastomosis had only one fourth major morbidity (2.3 percent versus 8.9 percent). Multivariate analysis revealed postoperation hospital stay, American Society of Anesthesiologists (ASA) score, number of positive lymph nodes had negative impact on OS, while R0, R1 surgical margin had protective effect on OS. Postoperative hospital stay had negative impact on PFS, while primary closure, end-end anastomosis, short-term vascular patency, and short-term vascular stenosis positively related to PFS. CONCLUSIONS: In LPD-MPVRs, interposition graft had the worst OS, the worst PFS, the highest rate of major morbidity, and the highest rate of 90-day mortality. While there were no differences in OS and PFS between primary closure and end-end anastomosis.

Laparoscopic revision of duct-to-mucosa pancreaticojejunostomy anastomotic stricture after laparoscopic pancreaticoduodenectomy.

PURPOSE: Pancreaticojejunostomy stricture (PJS) is an uncommon late complication of laparoscopic pancreaticoduodenectomy (LPD). The incidence, clinical characteristics, and managements of PJS after LPD are still unreported. METHODS: All patients undergoing LPD between January 2015 and December 2019 were identified from an institutional database. All pancreaticojejunostomies were performed using Bing's duct-to-mucosa anastomosis. PJS was diagnosed by computed tomography or magnetic resonance cholangio-pancreatography with secretin administration. Re-operation was performed in those patients with persistent abdominal pain and/or recurrent pancreatitis. Patients' demographic characteristics, perioperative outcomes, and follow-up outcomes were retrospectively collected. RESULTS: During the 5-year study period, 506 cases of LPD were performed. Among these patients, 13 patients (2.6%) were diagnosed with PJS. Only seven patients presented with abdominal pain and/or recurrent pancreatitis and underwent re-operation. The interval between the diagnosis of PJS and the original operation was 23 months. The median operative time was 140 min (range 90 to 210 min). The estimated blood loss was 40 ml (range 10 to 100 ml). The post-operative outcomes were favorable. Only one patient suffered from biochemical fistula. Six of these 7 patients (85.7%) reported complete pain resolution after the re-operation. The other patient reported partial resolution after surgery. All patients did not need to take analgesic drugs after the operation. CONCLUSION: PJS following LPD is a late complication that was underestimated. It is technically safe and clinically effective to perform laparoscopic revision of the PJS after LPD.

Initial experience of single-incision plus one port total laparoscopic pancreaticoduodenectomy.

BACKGROUND: The use of single-incision plus one-port laparoscopic pancreaticoduodenectomy (SILPD + 1) has been never reported, and its safety and efficacy remain unknown. This study aimed to evaluate the short-term outcomes of SILPD + 1 compared with those of conventional laparoscopic pancreaticoduodenectomy (CLPD). METHOD: Fifty-seven cases of laparoscopic pancreaticoduodenectomy (LPD) were performed between November 2021, and March 2022. Among them, 10 cases of LPD were performed using a single-incision plus one-port device. Based on the same inclusion and exclusion criteria, 47 cases of LPD performed using traditional 5-trocar were included as a control group. The patient's demographic characteristics, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. RESULTS: Three men and seven women were included in the SILPD + 1 group. All baseline parameters of both groups were comparable, except for age. Patients were younger in the SILPD + 1 group (47.2 ± 18.3 years vs. 60.6 ± 11.7 years, P = 0.05) than that in the CLPD group. Compared with the CLPD group, median operation time (222.5 (208.8-245.0) vs. 305.0 (256.0-37.0) min, P < 0.001) was shorter, median postoperative VAS scores on days 1-3 were lower, and median cosmetic score (21.0 (19.0-23.5) vs. 17.0 (16.0-20.0), P = 0.026) was higher one month after the surgery in the SILPD + 1 group. The estimated blood loss, conversion rate, blood-transfusion rate, exhaust time, time of drainage tube removal, postoperative hospital stays, and perioperative complications were comparable between the two groups. CONCLUSION: In a high-volume LPD center, SILPD + 1 is safe and feasible for well-selected patients without increasing the operation time and complications. It even has the advantages of reduced postoperative pain and improved cosmetic results.

Laparoscopic parenchyma-sparing resections for solid pseudopapillary tumors located in the head of pancreas.

BACKGROUND: Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. Here, we aimed to determine the safety and feasibility of laparoscopic parenchyma-sparing pancreatectomy for SPT located in the pancreatic head. METHODS: From July 2014 to February 2022, 62 patients with SPT located in the pancreatic head were operated laparoscopically in two institutions. These patients were divided into two groups according to the operative strategy: laparoscopic parenchyma-sparing pancreatectomy (27 patients, group 1) and laparoscopic pancreaticoduodenectomy (35 patients, group 2). The clinical data were retrospectively collected and analyzed in terms of demographic characteristics, perioperative variables, and long-term follow-up outcomes. RESULTS: The demographic characteristics of the patients in the two groups were comparable. Compared to the patients in group 2, those in group 1 required less operative time (263.4 ± 37.2 min vs. 332.7 ± 55.6 min, p < 0.001) and experienced less blood loss (105.1 ± 36.5mL vs. 188.3 ± 150.7 mL, p < 0.001). None of the patients in group 1 had tumor recurrence or metastasis. However, 1 (2.5%) patient in group 2 showed liver metastasis. CONCLUSION: Laparoscopic parenchyma-sparing pancreatectomy is a safe and feasible approach for SPT located in the pancreatic head, with favorable long-term functional and oncological results.

Clinical observation and finite element analysis of femoral stable interlocking intramedullary nail in intertrochanteric fractures.

PURPOSE: This study was designed to compare clinical outcomes of the femoral stable interlocking intramedullary nail (FSIIN) with proximal femoral nail anti-rotation (PFNA) for the treatment of intertrochanteric fractures (OTA 31A1 + A2). METHODS: This study retrospectively analyzed a registered sample of 74 intertrochanteric fractures (OTA 31A1 + A2) surgically treated using FSIIN (n = 36) or PFNA (n = 38) from January 2015 to December 2021. The intra-operative variables (operation time, fluoroscopy time, intra-operative blood loss, length of incision) and fracture healing time were compared between the two groups in this study. Harris hip score (HHS) and visual analog scale (VAS) were used to evaluate the functional states. At the last follow-up, the incidence of related complications in patients was calculated. Eventually, the 3D finite element model was established to analyze the stress of FSIIN and PFNA. RESULTS: The distribution of all basic characteristics was similar between the two groups (p > 0.05). The operation time, fluoroscopy time, intra-operative blood loss, and length of incision were significantly decreased in the FSIIN group (p < 0.001). The FSIIN group had a shorter fracture healing time than the PFNA group (p < 0.001). There is no significant difference between the two groups in the Harris and VAS (p > 0.05). The incidences of post-operative anaemia, electrolyte imbalance, varus malalignment, and thigh pain were significantly lower in FSIIN than in PFNA groups (all p < 0.05). The finite element results show that the stress shielding effect of FSIIN is smaller. CONCLUSIONS: Our study revealed that FSIIN seemed to be superior to PFNA in the treatment of intertrochanteric fractures (OTA 31A1 + A2) due to less surgical damage and shorter fracture healing time.

Gas-Pressurized Torrefaction of Lignocellulosic Solid Wastes: Deoxygenation and Aromatization Mechanisms of Cellulose.

A novel gas-pressurized (GP) torrefaction method at 250 °C has recently been developed that realizes the deep decomposition of cellulose in lignocellulosic solid wastes (LSW) to as high as 90% through deoxygenation and aromatization reactions. However, the deoxygenation and aromatization mechanisms are currently unclear. In this work, these mechanisms were studied through a developed molecular structure calculation method and the GP torrefaction of pure cellulose. The results demonstrate that GP torrefaction at 250 °C causes 47 wt.% of mass loss and 72 wt.% of O removal for cellulose, while traditional torrefaction at atmospheric pressure has almost no impact on cellulose decomposition. The GP-torrefied cellulose is determined to be composed of an aromatic furans nucleus with branch aliphatic C through conventional characterization. A molecular structure calculation method and its principles were developed for further investigation of molecular-level mechanisms. It was found 2-ring furans aromatic compound intermediate is formed by intra- and inter-molecular dehydroxylation reactions of amorphous cellulose, and the removal of O-containing function groups is mainly through the production of H2O. The three-ring furans aromatic compound intermediate and GP-torrefied cellulose are further formed through the polymerization reaction, which enhances the removal of ketones and aldehydes function groups in intermediate torrefied cellulose and form gaseous CO and O-containing organic molecules. A deoxygenation and aromatization mechanism model was developed based on the above investigation. This work provides theoretical guidance for the optimization of the gas-pressurized torrefaction method and a study method for the determination of molecular-level structure and the mechanism investigation of the thermal conversion processes of LSW.

Chromosomal genome and population genetic analyses to reveal genetic architecture, breeding history and genes related to cadmium accumulation in Lentinula edodes.

BACKGROUND: Lentinula edodes (Berk.) is the second most productive mushroom in the world. It contains compounds effective for antiviral, antitumor, antioxidant and immune regulation. Although genomes have previously been reported for this species, a high-quality chromosome-level reference for L. edodes is unavailable. This hinders detailed investigation of population genetics, breeding history of strains and genes related to environmental stress responses. RESULTS: A high-quality chromosome-level genome was constructed. We separated a monokaryon from protoplasts of the commercial L. edodes strain L808 and assembled the genome of L. edodes using PacBio long-read and Illumina short-read sequencing, along with the high-throughput chromatin conformation capture (Hi-C) technique. We assembled a 45.87 Mb genome, and 99% of the sequences were anchored onto 10 chromosomes. The contig and scaffold N50 length were 2.17 and 4.94 Mb, respectively. Over 96% of the complete Benchmarking Universal Single-Copy Orthologs (BUSCO) were identified, and 9853 protein-coding genes were predicted. We performed population genome resequencing using 34 wild strains and 65 commercial cultivars of L. edodes originating from China, Japan, the United States and Australia. Based on whole-genome variants, we showed substantial differences in the Chinese wild population, which divided into different branches according to the main areas of their geographical distribution. We also determined the breeding history of L. edodes at the molecular level, and demonstrated that the cultivated strains in China mainly originated from wild strains from China and Northeast Asia. Phenotypic analysis showed that 99 strains exhibited differences on the Cd accumulation. Three significant loci in the of L. edodes genome were identified using the genome-wide association study (GWAS) of Cd accumulation traits. Functional genes associated with Cd accumulation traits were related to DNA ligase and aminoacyl tRNA synthetase, indicating that DNA damage repair and in vivo protein translation may be responses to Cd stress. CONCLUSIONS: A high-quality chromosome-level genome and population genetic data of L. edodes provide genetic resources for functional genomic, evolutionary and artificial breeding studies for L. edodes.

Goslin 2.0 Implements the Recent Lipid Shorthand Nomenclature for MS-Derived Lipid Structures.

Goslin is the first grammar-based computational library for the recognition/parsing and normalization of lipid names following the hierarchical lipid shorthand nomenclature. The new version Goslin 2.0 implements the latest nomenclature and adds an additional grammar to recognize systematic IUPAC-IUB fatty acyl names as stored, e.g., in the LIPID MAPS database and is perfectly suited to update lipid names in LIPID MAPS or HMDB databases to the latest nomenclature. Goslin 2.0 is available as a standalone web application with a REST API as well as C++, C#, Java, Python 3, and R libraries. Importantly, it can be easily included in lipidomics tools and scripts providing direct access to translation functions. All implementations are open source.