Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Analysis of the Correlation between Persimmon Fruit-Sugar Components and Taste Traits from Germplasm Evaluation.

Persimmon fruits are brightly colored and nutritious and are fruits that contain large amounts of sugar, vitamins, mineral elements, and phenolic substances. The aim of this study was to explore the differences in fruit-sugar components of different persimmon germplasms and their relationships with phenotypic and flavor indices through the determination of phenotypes and sugar components and through electronic-tongue indices, which provided the basis and inspiration for the selection of different sugar-accumulating types of persimmon fruits and the selection of high-sugar persimmon varieties. Our results showed that persimmon germplasm fruit-sugar components were dominated by sucrose, glucose and fructose and that the remaining sugar components were more diverse but less distributed among the various germplasm types. Based on the proportion of each sugar component in the fruit, persimmon germplasms can be categorized into sucrose-accumulating and reduced-sugar-accumulation types. Sucrose-accumulating types are dominated by sucrose, galactose, fucose and inositol, while reduced-sugar-accumulation types are dominated by glucose, fructose, mannose-6-phosphate, and xylose. The content of sugar components in the germplasm persimmon of fruits of different types and maturity periods of also differed, with significant differences in sugar components between PCNA (pollination-constant non-astringent) and PCA (pollination-constant astringent) fruits. Cluster analysis classified 81 persimmon germplasms into three clusters, including cluster I-A, with low glucose and fructose content, and cluster I-B, with medium glucose, fructose, and sucrose contents. Cluster II was high in sucrose and fructose. Cluster III had high contents of glucose and fructose and low contents of sucrose and inositol.

Versatile Fabrication of Polymer Microcapsules with Controlled Shell Composition and Tunable Performance via Photopolymerization.

In this work, a series of polymer microcapsules based on UV-curable prepolymers are prepared by combining an emulsion template and photopolymerization. The modulation of the shell structure is achieved by employing UV-curable prepolymers with different chemical structures (polyurethane acrylates, polyester acrylates, and epoxy acrylates) and functionalities (di-, tetra-, and hex-). The relationships between the shell structure and the microcapsule properties are investigated in detail. The results show that the properties of the microcapsules can be effectively regulated by adjusting the composition and cross-linking density of the shell. Epoxy acrylate-based microcapsules exhibit higher impermeability, solvent resistance, and barrier and mechanical properties than polyurethane acrylate and polyester acrylate-based microcapsules. Using UV-curable prepolymer with high functionality as a shell-forming material could effectively improve the impermeability, solvent resistance, and barrier and mechanical properties of microcapsules. In addition, the dispersion of microcapsules in the coating matrix tends to follow the "similar component, better compatibility" principle, i.e., a uniform dispersion of the microcapsule in the coating matrix is more easily achieved when the compositions of the microcapsule shell and coating are similar in structure. The convenient adjustment of the shell structure and the investigation of the "structure-property" relationship provide guidance for the further controlled design of microcapsules.

A facile one-pot strategy for the preparation of porous polymeric microspheres via UV irradiation-induced polymerization in emulsions.

In this study, a facile one-pot strategy was developed to prepare porous polymeric microspheres via photopolymerization, where organic solvents functioned as porogens. In this strategy, an oil phase containing organic solvents and photopolymerizable materials was stabilized in water to form a stable oil-in-water emulsion. Upon UV irradiation, the photopolymerizable materials (photosensitive monomers/photosensitive prepolymers) underwent polymerization to form microspheres and the subsequent removal of organic solvents left pores in microspheres, leading to the generation of porous polymeric microspheres with high yielding. The effects of organic solvents and the chemical structure and concentration of photopolymerizable materials on the microsphere structure were systematically explored. It was found that the polarity of the organic solvents played a decisive role in the preparation of porous microspheres. In addition, the increases in the solvent content and functionalities of photopolymerizable materials were more favorable for the generation of porous microspheres. This strategy could be applicable for a wide selection of photopolymerizable materials, which endowed this strategy with good applicability. The preparation of porous microspheres by this method was facile and easy to handle, enabling the scalable preparation of porous microspheres. In addition, the whole process can be completed within a few minutes at ambient temperature, which was time-saving and energy-saving.

Use of human fibrin glue (Tisseel) versus suture during transvaginal natural orifice ovarian cystectomy of benign and non-endometriotic ovarian tumor: a retrospective comparative study.

BACKGROUND: To evaluate the use of a human fibrin glue (Tisseel) for minor bleeding control and approximation of ovarian defect during transvaginal natural orifice ovarian cystectomy (TNOOC) of benign and non-endometriotic ovarian tumors. METHODS: A total of 125 women with benign and non-endometriotic ovarian tumors who underwent TNOOC between May 2011 and January 2020: 54 with the aid of Tisseel and 71 with traditional suture for hemostasis and approximation of ovarian defect. Surgical outcomes such as length of surgery, operative blood loss, postoperative pain score, and postoperative hospital stay were recorded. Before and immediately (10 days) and at 6 months after the procedure, serum anti-Müllerian hormone (AMH) levels were also determined. RESULTS: Complete hemostasis and approximation of ovarian defect were achieved in all cases. No significant difference was noted in the operating time, operative blood loss, postoperative pain scores after 12, 24 and 48 h, length of postoperative stay, and baseline AMH levels between the two groups. The operation did not have a negative effect on the immediate and 6-month postoperative AMH levels in the suture group. However, the decline in the AMH levels was significant immediately after surgery in the Tisseel group, nevertheless, no significant difference was noted in the AMH levels at 6 months (3.3 vs. 1.7 mg/mL; p = 0.042, adjusted p = 0.210). CONCLUSION: The use of Tisseel in TNOOC of benign and non-endometriotic ovarian tumors without suturing the ovarian tissue is clinically safe and feasible.

Learning Curve Analysis of Transvaginal Natural Orifice Adnexal Surgery.

STUDY OBJECTIVE: This study was designed to evaluate the learning curve of transvaginal natural orifice surgery (NOS) for adnexal tumors based on the type of procedure (adnexectomy or cystectomy). DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENTS: One hundred thirty-six women with adnexal tumors. INTERVENTIONS: A series of 136 consecutive transvaginal NOS for adnexal tumor were performed between April 2011 and June 2016. Eighty-five patients (62.5%) had undergone cystectomy, and 51 patients (37.5%) had undergone adnexectomy. MEASUREMENTS AND MAIN RESULTS: The transvaginal NOS procedures included vaginal, endoscopic, single-port access techniques and were divided into 2 categories: adnexectomy and cystectomy. Operating time was electronically recorded and was defined as the time from the creation of a posterior colpotomy incision until the complete closure of the posterior colpotomy opening. The average operating time for the cystectomy and adnexectomy groups was 42.7 and 37.7 minutes, respectively (p = .015). The learning curve was analyzed using the cumulative summation method and showed that 36 cases were needed to achieve proficiency in transvaginal NOS for ovarian cystectomy. However, there was no significant cut-off point to determine the number of patients who had undergone adnexectomy. CONCLUSION: A well-trained gynecologic endoscopist can achieve surgical proficiency in transvaginal NOS cystectomy after 36 cases. It is suggested that the surgical transvaginal NOS procedure should begin with adnexectomy rather than with cystectomy to avoid initial technical challenges.

A Simple Technique for the Placement of Seprafilm, a Sodium Hyaluronate or Carboxymethylcellulose Absorbable Barrier, during Laparoscopic Myomectomy.

This report describes a simple technique using conventional instrumentation for the placement of Seprafilm, a sodium hyaluronate or carboxymethylcellulose absorbable barrier for adhesion prevention. A total of 378 women with uterine myomas undergoing laparoscopic myomectomies had 737 Seprafilm pieces placed. Seprafilm sheet was softened through exposure to room air for 5 minutes, cut into 4 pieces (length, 5-10 mm), rolled up alongside a plastic sheet cut from a camera drape cover, and gently placed at the right paracolic gutter. The Seprafilm pieces unfolded semiautomatically on release and were then placed on the uterus. The median time to apply per Seprafilm piece was 1 (range: 0.8-3.5) minute. We failed to place 16 pieces (16 of 737, 2.2%) in 11 patients. Virginal status, myoma weight, and the number of removed myomas were the risk factors of failed placement. Our technique for Seprafilm placement during laparoscopic myomectomy is simple and safe.

Novel Neovaginoplasty Using Rudimentary Uterine Horn Serosa and Pelvic Peritoneum as a Graft in Müllerian Anomalies with Vaginal Agenesis.

STUDY OBJECTIVE: To study the outcome of a novel method of laparoscopic neovaginal reconstruction using rudimentary uterine horn serosa and the pelvic peritoneum as a graft. DESIGN: Canadian Task Force classification II-1. SETTING: A university hospital. PATIENTS: A retrospective study of 14 patients from 2000 to 2014 of patients with vaginal agenesis who underwent laparoscopic neovagina reconstruction using rudimentary uterine horn serosa and the pelvic peritoneum as a graft. INTERVENTION: Patients with vaginal agenesis associated with müllerian agenesis who requested surgery. Tertiary referral center and laparoscopic unit. The creation of a neovagina using rudimentary uterine horn serosa and the pelvic peritoneum as a graft via a combined laparoscopic and vaginal route. MEASUREMENTS AND MAIN RESULTS: Data were collected retrospectively including postoperative vaginal length and width, complications, stenosis or reoperations, dyspareunia, and sexual satisfaction. There were no major complications from the surgery with no rectal perforation or bladder or ureteric injury. The postoperative mean (±SD) vaginal length was 6.0±0.7 cm and a width of 2 fingerbreadths. The mean operation time was 142.7±45.9 min. Median blood loss was 100 ml (range: 10 to 300 mL). The mean duration of the hospital stay was 6.6±1.6 days. The follow-up period ranged from 3 to 84 months with a median follow-up of 11 months. CONCLUSION: Lee's method of neovaginoplasty using rudimentary uterine horn serosa and the pelvic peritoneum as a graft is a good method for neovagina creation with minimal morbidity, fast recovery, and minimal complications. This method results in good anatomic and functional outcome and can be a method that is widely used.

Learning curve analysis of transvaginal natural orifice transluminal endoscopic hysterectomy.

BACKGROUND: No data are available to assess the learning curve for transvaginal natural orifice transluminal endoscopic hysterectomy for non-prolapsed uteri in benign gynecologic diseases. The lack of exposure to transvaginal natural orifice transluminal endoscopic hysterectomy during training, in addition to a poorly defined learning curve, further deters interested physicians from applying this technique to daily practice. The aim of this study was to evaluate the learning curve and perioperative outcome of transvaginal natural orifice transluminal endoscopic hysterectomy by an experienced endoscopist. METHODS: A total of 240 cases of transvaginal natural orifice transluminal endoscopic hysterectomies with or without adnexectomy for various benign gynecologic diseases were included. Demographic data and various perioperative parameters were reviewed from the prospectively collected database. Operative time was set as a surrogate marker for surgical competency. The learning curve was evaluated using the cumulative sum method. RESULTS: The overall mean operative time (OT) was 76.5 min ± 22.4. Four unique phases of the learning curve were derived using cumulative sum analysis: the mean OT of phase I (the initial learning curve of 20 cases) was 86.3 ± 23.7 min, phase II (acquisition of competence of 80 cases) was 71.0 ± 21.4 min, phase III (proficiency and plateau of 80 cases) was 76.0 ± 20.4 min, and phase IV (post-learning in which more challenging cases were managed) was 81.3 ± 23.6 min. No major complications were encountered. One case in phase III converted to laparoscopy due to difficulty in performing anterior colpotomy. CONCLUSION: Our data demonstrated four distinct phases of the learning curve of transvaginal natural orifice transluminal endoscopic hysterectomy. In a well-trained endoscopist, surgical competence in transvaginal natural orifice transluminal endoscopic hysterectomy can be reached after 20 cases.

Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (NOTES): a series of 137 patients.

STUDY OBJECTIVE: To evaluate the feasibility and safety of hysterectomy in benign disease using transvaginal natural orifice transluminal endoscopic surgery (NOTES). DESIGN: Prospective observational study (Canadian Task Force classification II-3). SETTING: Tertiary referral medical center. PATIENTS: From May 2010 to August 2011, consecutive patients who were scheduled to undergo laparoscopic hysterectomy and without virginity or suspected pelvic inflammation or cul-de-sac obliteration were included. INTERVENTION: Total hysterectomy via transvaginal NOTES. MEASUREMENTS AND MAIN RESULTS: The study included 137 patients, with mean (SEM) age 46.0 (0.4) years and body mass index 24.7 (0.4). Transvaginal NOTES was successfully performed in 130 patients (94.9%). Fifteen patients underwent concurrent adhesiolysis, and 17 underwent adnexal procedures. Mean (SEM) uterine weight was 450.0 (24.1) g; in 45 patients (34.6%), uterine weight was >500 g, and in 7 (5.4%) it was >1000 g. Operative time was 88.2 (4.1) minutes, with blood loss of 257.7 (23.9) mL. In 2 patients there was intraoperative hemorrhage or unintended cystotomy, and in another 5 transvaginal colpotomy failed because of a narrow vagina, cul-de-sac obliteration by bowel adhesions, or mass obstruction. Complications in these 7 patients (5.1%) were successfully managed via transabdominal laparoscopy. Five patients (3.6%) experienced postoperative urinary retention or febrile morbidity, and recovered uneventfully with conservative treatment. CONCLUSION: Transvaginal NOTES is a feasible technique for performance of hysterectomy and can be used in procedures that are difficult to complete via conventional vaginal surgery because posterior colpotomy is achievable. This procedure was not impeded by uterine volume, and had the advantage of no abdominal incision.

Aggregation structure induced by heat treatments mediated the gastric digestion behavior of soybean protein.

The common belief that heat treatment enhances the gastric digestion of proteins is largely based on findings from animal proteins and may not apply to all proteins, particularly plant proteins. Here, we compared the digestion characteristics of soybean protein isolates (SPI) in an in vitro semi-dynamic digestion model and found distinct effects of heat treatment on the digestion properties of plant proteins. The results revealed that heat-treated SPIs formed clots during the early stages of digestion, although the clots gradually became smaller and looser as digestion progressed, the systems remained turbid at the end of gastric digestion, indicating the lag in their emptying. Furthermore, heat treatment altered the rheological properties of SPI, resulting in increased viscosity and slower gastric emptying. These effects became more pronounced with increasing heat treatment temperatures. The fluorescence spectrum analysis indicated that heat treatment altered its conformation. This led to protein unfolding and exposure of hydrophobic groups, facilitating the formation of larger aggregates during digestion. Additionally, heat treatment exposed more cleavage sites for gastric proteases, increasing the extent of hydrolysis. Elevated levels of free amino acids and a smaller molecular weight distribution further corroborated these findings. These findings contribute to a deeper understanding of the gastric digestion characteristics of plant proteins and the relationship between protein aggregation structure and the digestion process.

Preparation of Graphene Oxide/Polymer Hybrid Microcapsules via Photopolymerization for Double Self-Healing Anticorrosion Coatings.

In this work, graphene oxide (GO)/polymer hybrid microcapsule-loaded self-healing agents were prepared via the combination of the emulsion template method and photopolymerization technology. The incorporation of GO in the microcapsule shell not only improved the impermeability, mechanical property, and solvent resistance property of the microcapsules significantly but also endowed the microcapsules with photothermal conversion property. By incorporating GO/polymer hybrid microcapsules in water-borne epoxy resin, a novel kind of anticorrosion coating with a double self-healing property was successfully fabricated. When the coating was scratched, the linseed oil (LO) encapsulated in the microcapsules could fill the crack, and the photothermal conversion property of GO could promote the molecular chain movement of the damaged area under near-infrared (NIR) irradiation to realize the close of the crack. Based on the filling of LO and photothermal conversion-induced scratch narrowing, the "filling" and "close" double self-healing effect can be realized under temporal NIR irradiation, which could lead to the complete recovery of the scratched coating. The |Z|f=0.1Hz value of the damaged coating with GO/polymer microcapsules after double healing was comparable to that of the intact coating, which was about 4 orders of magnitude higher than that of the scratched blank coating and single self-healing coating. As to the neutral salt spray test, the scratched blank coating failed in protection after 100 h, while the healed composite coating did not show any corrosion after 300 h.

Digestion behavior of plant-based meat analogs with anisotropic fibrous structure in a semi-dynamic gastric digestion system.

Plant-based meat analogs have increasingly attracted the attention of the food industry in recent years. However, the digestion behavior of this innovative solid food in human stomach is poorly understood. In this study, plant-based meat analogs with different internal structures were prepared with/without high-moisture extrusion technology and at different temperatures. A semi-dynamic gastric digestion system which involves the mimic processes of the secretion of gastric juice and the gastric emptying was applied. After extrusion treatment at high temperature (150 ℃), the EHT had the highest anisotropic index (H⊥/H∥=1.90) and an ideal meat-like structure. It was found that particle disintegration and swelling simultaneously occurred in the bolus of the EHT but not in the sample without extrusion treatment (the HLT) in the early stage of gastric digestion. This difference might be attributed to the compact and well-arranged anisotropic structure of the EHT resulting from the extrusion, and leads to difficult enzymatic hydrolyzation unless the particles swell and unfold the polymer chains. The difficulty in particle disintegration in the EHT during gastric digestion is the consequence of the relatively slow gastric emptying rate and the decrease of protein degradation. As a result, the EHT which underwent extrusion treatment at high temperature and possessed the best anisotropic fibrous structure exhibited the slowest gastric digestion. This novel solid food shows good potential as a desired nutritional food for people on diet.

Evaluation of a novel vaginal cells self-sampling device for human papillomavirus testing in cervical cancer screening: A clinical trial assessing reliability and acceptability.

Cervical cancer is a significant public health concern, particularly in low- and middle-income countries where resources for prevention and treatment are limited. Routine screening, such as the Papanicolaou test (Pap smears) and human papillomavirus (HPV) testing, plays a crucial role in the early detection and prevention of cervical cancer. However, the participation rate in cervical cancer screening programs remains below optimal levels due to various factors. This study aimed to evaluate the reliability and acceptability of the HygeiaTouch Self Sampling Kit for Women in collecting vaginal samples for HPV typing, comparing the results with samples collected by physicians. The study included 1210 women aged 21-65 from three medical centers in Taiwan. The findings indicated that the self-sampling kit was as effective as physician-collected specimens in terms of obtaining valid samples and identifying HPV. The agreement between the two methods was 88%, with a κ value of 0.75. Furthermore, the study assessed the mechanical characteristics of the self-sampling applicator through tensile, bending, and torque tests, and determined that it was safe for intravaginal use. Additionally, the study evaluated the safety and satisfaction of self-sampling and found a low rate of adverse events (0.7%) and high levels of satisfaction (over 90%) among participants. Overall, we demonstrated that the HygeiaTouch Self Sampling Kit for Women is a reliable and acceptable device for HPV testing and cervical screening, providing a convenient, safe, and effective alternative for women.

Neurotransmitter noradrenaline downregulate cytoskeletal protein expression of VSMCs.

OBJECTIVE: This study investigates the effects of noradrenaline (NA) on cytoskeletal protein expression of vascular smooth muscle cells (VSMCs). METHODS: VSMCs were isolated from rat aortic tissue and cultured. The cultured VSMCs were divided into 4 experimental groups: (1) control group, (2) NA treatment group, (3) starvation group, and (4) NA treatment+starvation group. The expression of cytoskeletal protein (smooth muscle α-actin, ß-tubulin and desmin) was evaluated by (i) Coomassie blue staining, (ii) immunofluorescent staining, and (iii) RT-PCR and Western Blot. RESULTS: NA treatment significantly downregulated the expression of SM α-actin, ß-tubulin and desmin (P<0.05). The serum starvation did not affect the expression of cytoskeletal protein (SM α-actin, ß-tubulin and desmin), but when the cells were treated with the combination of NA and serum starvation, the expression of SM α-actin, ß-tubulin and desmin were down-regulated than those of the serum starvation group (P<0.05). CONCLUSION: These results suggested that NA might play a key role in regulating the cytoskeletal protein expression of VSMCs.

Full-length transcriptome profiling for fruit development in Diospyros oleifera using nanopore sequencing.

OBJECTIVES: Diospyros oleifera, one of the most economically important Diospyros species, is an ideal model for studying the fruit development of persimmon. While, the lack of whole-transcriptome has hindered the complex transcriptional regulation mechanisms of sugar and tannin during fruit development. DATA DESCRIPTION: We applied Oxford Nanopore Technologies to six developmental stage of fruit from D. oleifera for use in transcriptome sequencing. As a result of full-length transcriptome sequencing, 55.87 Gb of clean data were generated. After mapping onto the reference genome of D. oleifera, 51,588 full-length collapsing transcripts, including 2,727 new gene loci and 43,223 transcripts, were obtained. Comprehensively annotated, 38,086 of new transcripts were functional annotation, and 972 lncRNAs, 7,159 AS events were predicted. Here, we released the transcriptome database of D. oleifera at different stage of fruit development,which will provide a fundamention of to investigatethe transcript structure, variants and evolution of persimmon.

The discovery of a new type of innervation in lymphoid organs.

It is well known that the main forms of innervation are synapses and free nerve endings, while other forms of innervation have not been reported. Here, we explore a new way of innervating lymphoid organs. Male Sprague-Dawley rats were used for studying the innervation of sympathetic nerve fibers in lymph nodes by means of anterograde tracking, immunoelectron microscopy, three-dimension reconstruction analysis, and immunofluorescence labeling. The results showed that the Fluoro-Ruby labeled nerve endings targeted only a group of cells in the lymph nodes and entered the cells through the plasma membrane. The electron microscopy showed that the biotinylated glucan amine reaction elements were distributed in the cytoplasm, and most of the biotinylated glucan amine active elements were concentrated on the microtubule and microfilament walls. Birbeck particles with rod-shaped and/or tennis racket like structures can be seen in the labeled cells at high magnification, and Birbeck particles contain biotinylated glucan amine-reactive elements. The immunofluoresence results showed that the Fluoro-Ruby-labeled nerve innervating cells expressed CD207 and CD1a protein. This result confirmed that the labeled cells were Langerhans cells. Our findings suggested that Langerhans cells might serve as a "bridge cell" for neuroimmune cross-talking in lymph organs, which play an important role in transmitting signals of the nervous system to immune system. This study also opened up a new way for further study of immune regulation mechanism.

Starvation-inactivated MTOR triggers cell migration via a ULK1-SH3PXD2A/TKS5-MMP14 pathway in ovarian carcinoma.

ABBREVIATIONS: AMPK: AMP-activated protein kinase; CHX: cycloheximide; RAD001: everolimus; HBSS: Hanks' balanced salt solution; LC-MS/MS: liquid chromatography-mass spectrometry/mass spectrometry; MMP14: matrix metallopeptidase 14; MTOR: mechanistic target of rapamycin kinase; MAPK: mitogen-activated protein kinase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; PtdIns3P: phosphatidylinositol-3-phosphate; PX: phox homology; SH3: Src homology 3; SH3PXD2A/TKS5: SH3 and PX domains 2A; SH3PXD2A-[6A]: S112A S142A S146A S147A S175A S348A mutant; ULK1: unc-51 like autophagy activating kinase 1.