Efficiency measurement and inefficiency analysis of low-carbon logistics in the Beijing-Tianjin-Hebei region, China.

Under the dual-carbon goals, enhancing the green development level of logistics industry and realizing its low-carbon transformation are important issues that need to be solved urgently. Amidst the continuous escalation in the total energy consumption of the national logistics industry, the Beijing-Tianjin-Hebei (BTH) region has exhibited a favorable descending trajectory in this respect. It is necessary to investigate the underlying reasons. Based on the panel data from 2012 to 2021, the DEA and Malmquist index are employed to analyze the low-carbon logistics efficiency of the BTH region from both static and dynamic perspectives. Furthermore, the inefficiency analysis is conducted to identify the deficiencies of low-carbon logistics industry in this region. Results show that (1) from the static perspective, the development of low-carbon logistics industry in the BTH region is relatively unbalanced. Compared to Tianjin and Hebei, Beijing's low-carbon logistics efficiency is significantly lower, becoming the focal area for attention; (2) from the dynamic perspective, technological progress is the main reason for the fluctuation of total factor productivity in the BTH region and a constraining factor for further improvements; (3) from the results of inefficiency analysis, the forthcoming emphasis on low-carbon logistics in Beijing should be on optimizing the number of logistics practitioners, transportation efficiency, and energy efficiency. Economic output and energy efficiency are relatively vulnerable aspects in Tianjin and Hebei, respectively, warranting due consideration. The research results of this paper have important practical implications for better developing low-carbon logistics in the BTH region and leveraging its leading role nationwide.

Hinokione: an abietene diterpene with pancreatic ß cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.

Concentration and composition of odd-chain fatty acids in phospholipids and triacylglycerols in Chinese human milk throughout lactation.

Human milk represents the gold standard for infant nutrition, with approximately 50% of the energy in human milk derived from lipids. Odd-chain fatty acids (OCFAs) have been recognized as a category of bioactive milk fatty acids in recent research; however, limited data exist on OCFAs in human milk. This study collected human milk samples spanning the postpartum period from 0 to 400 days. Phospholipids containing OCFAs (PL-OCFAs) were determined in 486 human milk samples using hydrophilic liquid chromatography-electrospray ionization-triquadrupole-mass spectrometry. Triacylglycerols containing OCFAs (TAG-OCFAs) were analyzed in 296 human milk samples using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The average total concentration of PL-OCFA ranged from 30.89 ± 14.27 mg L-1 to 93.48 ± 36.55 mg L-1 during lactation, and the average total TAG-OCFA content ranged from 103.1 ± 147.15 mg L-1 to 965.41 ± 651.67 mg L-1. Despite the lower absolute concentration of PL-OCFA, its relative concentration (8.75%-11.75%) was significantly higher than that of TAG-OCFA (0.37%-1.85%) throughout lactation. PC-OCFA, SM-OCFA and PE-OCFA are major sub-classes of PL-OCFA. Furthermore, C17:0 was the major chain length in both PL-OCFA and TAG-OCFA, followed by C15:0. C17:1 was characteristic of TAG-OCFA, while long-chain fatty acids C19:0, C21:0 and C23:0 were characteristic of PL-OCFA. Our findings highlighted the importance of bioactive lipids in human milk, suggesting that OCFAs could be targeted in future studies in relation to the health and development of infants.

Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

A novel GSK3ß inhibitor 5n attenuates acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality caused by various factor. The specific strategies for AKI are still lacking. GSK3ß is widely expressed in the kidneys. In acute models of injury, GSK3ß promotes the systemic inflammatory response, increases the proinflammatory release of cytokines, induces apoptosis, and alters cell proliferation. We screened a series of 3-(4-pyridyl)-5-(4-sulfamido-phenyl)-1,2,4-oxadiazole derivatives which are recognized as new GSK3ß inhibitors, and found that 5n had the least toxicity and the best cell protection. We then tested the anti-inflammatory and reno-protective effect of 5n in cisplatin-treated tubular epithelial cells. 5n had anti-inflammation effect indicated by phosphor-NF-κB detection. Finally, we found that 5n ameliorated renal injury and inflammation in cisplatin-induced AKI mouse model. Silencing GSK3ß inhibited cell injury and inflammation induced by cisplatin. We found that GSK3ß interacted with PP2Ac to modulate the activity of NF-κB. In conclusion, 5n, the novel GSK3ß inhibitor, protects against AKI via PP2Ac-dependent mechanisms which may provide a potential strategy for the treatment of AKI in clinic.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery.

BACKGROUND: This study was designed to investigate the clinical outcomes of enhanced recovery after surgery (ERAS) in the perioperative period in elderly patients with non-small cell lung cancer (NSCLC). AIM: To investigate the potential enhancement of video-assisted thoracic surgery (VATS) in postoperative recovery in elderly patients with NSCLC. METHODS: We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS (the ERAS group) and 327 elderly NSCLC patients who received routine care (the control group) after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017. After propensity score matching of baseline data, we analysed the postoperative stay, total hospital expenses, postoperative 48-h pain score, and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection. RESULTS: After propensity score matching, ERAS significantly reduced the postoperative hospital stay (6.96 ± 4.16 vs 8.48 ± 4.18 d, P = 0.001) and total hospital expenses (48875.27 ± 18437.5 vs 55497.64 ± 21168.63 CNY, P = 0.014) and improved the satisfaction score (79.8 ± 7.55 vs 77.35 ± 7.72, P = 0.029) relative to those for routine care. No significant between-group difference was observed in postoperative 48-h pain score (4.68 ± 1.69 vs 5.28 ± 2.1, P = 0.090) or postoperative complication rate (21.2% vs 27.1%, P = 0.371). Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection. CONCLUSION: ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Contralateral C7 nerve transfer in the treatment of central hemiplegia after stroke under general anesthesia: A case report.

Similar reports in the past pay less attention to the anesthetic management of these patients. We reported a 46-year-old man who suffered from hypertensive cerebral apoplexy 5 months ago and accepted C7 nerve transfer to improve the central spastic paralysis in the right upper limb. After careful evaluation and anesthesia management before anesthesia, the operation was successfully completed under general anesthesia. The patient was cured and discharged without complications. The anesthesia management of C7 nerve transfer should choose appropriate operation opportunities for patients according to the type of stroke, improve the preoperative preparation, and form a multidisciplinary diagnosis and treatment.

Compressed Sensitivity Encoding Artificial Intelligence Accelerates Brain Metastasis Imaging by Optimizing Image Quality and Reducing Scan Time.

BACKGROUND AND PURPOSE: Accelerating the image acquisition speed of MR imaging without compromising the image quality is challenging. This study aimed to evaluate the feasibility of contrast-enhanced (CE) 3D T1WI and CE 3D-FLAIR sequences reconstructed with compressed sensitivity encoding artificial intelligence (CS-AI) for detecting brain metastases (BM) and explore the optimal acceleration factor (AF) for clinical BM imaging. MATERIALS AND METHODS: Fifty-one patients with cancer with suspected BM were included. Fifty participants underwent different customized CE 3D-T1WI or CE 3D-FLAIR sequence scans. Compressed SENSE encoding acceleration 6 (CS6), a commercially available standard sequence, was used as the reference standard. Quantitative and qualitative methods were used to evaluate image quality. The SNR and contrast-to-noise ratio (CNR) were calculated, and qualitative evaluations were independently conducted by 2 neuroradiologists. After exploring the optimal AF, sample images were obtained from 1 patient by using both optimized sequences. RESULTS: Quantitatively, the CNR of the CS-AI protocol for CE 3D-T1WI and CE 3D-FLAIR sequences was superior to that of the CS protocol under the same AF (P < .05). Compared with reference CS6, the CS-AI groups had higher CNR values (all P < .05), with the CS-AI10 scan having the highest value. The SNR of the CS-AI group was better than that of the reference for both CE 3D-T1WI and CE 3D-FLAIR sequences (all P < .05). Qualitatively, the CS-AI protocol produced higher image quality scores than did the CS protocol with the same AF (all P < .05). In contrast to the reference CS6, the CS-AI group showed good image quality scores until an AF of up to 10 (all P < .05). The CS-AI10 scan provided the optimal images, improving the delineation of normal gray-white matter boundaries and lesion areas (P < .05). Compared with the reference, CS-AI10 showed reductions in scan time of 39.25% and 39.93% for CE 3D-T1WI and CE 3D-FLAIR sequences, respectively. CONCLUSIONS: CE 3D-T1WI and CE 3D-FLAIR sequences reconstructed with CS-AI for the detection of BM may provide a more effective alternative reconstruction approach than CS. CS-AI10 is suitable for clinical applications, providing optimal image quality and a shortened scan time.

Compounds from Agathis dammara exert hypoglycaemic activity by enhancing glucose uptake: lignans, terpenes and others.

In this study, two new kaurane diterpenes (16, 17), together with 12 lignans (1-12), a triterpene (15), and two other compounds (13, 14) were isolated from the woods of Agathis dammara. The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy, and its absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. Compounds 5, 11, 14 exhibit significant hypoglycaemic activity in zebrafish, and their mechanism of action is to enhance glucose uptake in zebrafish.

How does exotic Spartina alterniflora affect the contribution of iron-bound organic carbon to soil organic carbon in salt marshes?

Iron-bound organic carbon (OC-FeR) is important for the stability of soil organic carbon (SOC) in salt marshes, and the Spartina alterniflora invasion reshaped local salt marshes and changed the SOC pool. To evaluate the effects of S. alterniflora invasion on the contribution of OC-FeR to SOC, we determined the OC-FeR content and soil characteristics in the 0-50 cm soil profile along the vegetation sequence, including mudflats (MF), S. alterniflora marshes established in 2003 (SA03) and 1989 (SA89), the ecotone of S. alterniflora and Phragmites australis (SE), S. salsa marsh (SS), and P. australis marsh (PA). The SOC content was 6.55-17.5 mg g-1 in the S. alterniflora marshes. Reactive iron oxides (Fed, Feo, Fep) accumulated significantly in the S. alterniflora and P. australis salt marshes. PA and S. alterniflora marshes had higher DOC contents of 0.28-0.77 mg g-1. The OC-FeR content in the 0-50 cm soil profile in these ecosystems ranged from 0.3 to 3.29 mg g-1, with a contribution to the SOC content (fOC-FeR) of approximately 11 %, which was highest in SA03 (16.3 % ~ 18.8 %), followed by SA89, SE, and PA. In addition, the molar ratios of OC-FeR to Fed were <1, indicating that the iron oxides were associated with SOC through sorption more than coprecipitation. According to the structural equation model, SOC, DOC and iron oxides were the direct driving factors of OC-FeR formation, while the vegetation zone indirectly functioned by regulating organic C inputs, iron oxide formation, and pH. This study suggested that S. alterniflora invasion promotes iron-bound organic carbon accumulation by increasing organic C inputs and regulating iron oxide formation in salt marshes, but such promotion will degenerate with development duration.

Comparison of clinical features and outcomes between two age groups of cryptorchidism testicular torsion in children: a retrospective study in single center.

Objective: The purpose of this study was to compare the clinical characteristics and outcomes of children with cryptorchidism testicular torsion between the younger age group and the older age group. Methods: We collected the clinical data of children with cryptorchidism complicated with testicular torsion in our hospital from January 1, 2013 to January 1, 2023. The patients were divided into two groups: the younger age group (1month∼4 years old, n = 7) and the older age group (4∼18 years old, n = 7). The differences of clinical manifestations and surgical results between the two groups were compared. Results: A total of 14 patients with unilateral cryptorchidism testicular torsion were included in this study, including 9 on the left side and 5 on the right side. The main clinical manifestations were pain /swelling of groin. The rate of crying in the younger age group was significantly higher than those in the older age group [(5,71.4%) vs. (0,0.0%), P < 0.05]. The median duration of symptoms of the younger group was less than the older group [42(7,96) h vs. 70(24, 96) h, P > 0.05]. The ipsilateral testicular salvage rate in the younger age group was 14.3% (1/7), which was lower than the older age group 57.1% [(4/7), P > 0.05]. The degree of testicular torsion in younger age group was more severe than the older age group [720(360, 1,080)° vs. 360(270, 360)°, P > 0.05]. Conclusions: The overall salvage rate of cryptorchidism testicular torsion is low. Although the duration of symptoms in the older age group was longer, the salvage rate of the older age group seemed to be higher than that in the younger age group. In addition, physical and imaging examination of the reproductive system should be carried out in time to identify the children with cryptorchidism testicular torsion in the early stage.

Preparation of Antimony-Doped Tin Oxide Fly Ash Antistatic Composite and Its Properties in Filling EVA.

As a common coal-based solid waste, fly ash is widely used in material filling. However, due to the high resistivity of fly ash itself, the antistatic performance of the filling material is poor. Therefore, antistatic composite powder was prepared by coating nano-sized antimony-doped tin oxide (ATO) on the surface of fly ash, and its preparation mechanism was discussed. The composite powders were characterized by SEM, EDS, XRD and FTIR. The results show that the interaction between SiO2 and SnO2 appears at the wave number of 727.12 cm-1, and the obvious SnO2 crystal phase appears on the surface of fly ash. The volume resistivity of calcined fly ash is 1.72 × 1012 Ω·cm, and the volume resistivity of ATO fly ash is reduced to 6 × 103 Ω·cm. By analyzing the limiting oxygen index, melt index, tensile strength, elongation at break, cross-section morphology and surface electrical resistivity of EVA, it was found that the addition of antistatic powder to EVA can improve its antistatic performance without deteriorating the mechanical properties of EVA.

Genome sequences and population genomics reveal climatic adaptation and genomic divergence between two closely related sweetgum species.

Understanding the genetic basis of population divergence and adaptation is an important goal in population genetics and evolutionary biology. However, the relative roles of demographic history, gene flow, and/or selective regime in driving genomic divergence, climatic adaptation, and speciation in non-model tree species are not yet fully understood. To address this issue, we generated whole-genome resequencing data of Liquidambar formosana and L. acalycina, which are broadly sympatric but altitudinally segregated in the Tertiary relict forests of subtropical China. We integrated genomic and environmental data to investigate the demographic history, genomic divergence, and climatic adaptation of these two sister species. We inferred a scenario of allopatric species divergence during the late Miocene, followed by secondary contact during the Holocene. We identified multiple genomic islands of elevated divergence that mainly evolved through divergence hitchhiking and recombination rate variation, likely fostered by long-term refugial isolation and recent differential introgression in low-recombination genomic regions. We also found some candidate genes with divergent selection signatures potentially involved in climatic adaptation and reproductive isolation. Our results contribute to a better understanding of how late Tertiary/Quaternary climatic change influenced speciation, genomic divergence, climatic adaptation, and introgressive hybridization in East Asia's Tertiary relict flora. In addition, they should facilitate future evolutionary, conservation genomics, and molecular breeding studies in Liquidambar, a genus of important medicinal and ornamental values.

Deficiency of Trex1 leads to spontaneous development of type 1 diabetes.

BACKGROUND: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. METHODS: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-ß were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. RESULTS: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1-/- rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-ß, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic ß cells. CONCLUSIONS: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

Microenvironment-induced CREPT expression by cancer-derived small extracellular vesicles primes field cancerization.

Rationale: Cancer local recurrence increases the mortality of patients, and might be caused by field cancerization, a pre-malignant alteration of normal epithelial cells. It has been suggested that cancer-derived small extracellular vesicles (CDEs) may contribute to field cancerization, but the underlying mechanisms remain poorly understood. In this study, we aim to identify the key regulatory factors within recipient cells under the instigation of CDEs. Methods: In vitro experiments were performed to demonstrate that CDEs promote the expression of CREPT in normal epithelial cells. TMT-based quantitative mass spectrometry was employed to investigate the proteomic differences between normal cells and tumor cells. Loss-of-function approaches by CRISPR-Cas9 system were used to assess the role of CREPT in CDEs-induced field cancerization. RNA-seq was performed to explore the genes regulated by CREPT during field cancerization. Results: CDEs promote field cancerization by inducing the expression of CREPT in non-malignant epithelial cells through activating the ERK signaling pathway. Intriguingly, CDEs failed to induce field cancerization when CREPT was deleted, highlighting the importance of CREPT. Transcriptomic analyses revealed that CDEs elicited inflammatory responses, primarily through activation of the TNF signaling pathway. CREPT, in turn, regulates the transduction of downstream signals of TNF by modulating the expression of TNFR2 and PI3K, thereby promoting inflammation-to-cancer transition. Conclusion: CREPT not only serves as a biomarker for field cancerization, but also emerges as a target for preventing the cancer local recurrence.

Pathologic myopia in highly myopic patients with high axial anisomyopia.

PURPOSE: To determine prevalence of anisomyopia (axial length (AL) difference ≥2.5 mm) among high myopes ((HMs), defined by spherical equivalent of ≤6.0 diopters or AL ≥ 26.5 mm). To characterise the shorter anisomyopic eye (SAE) and evaluate if pathologic myopia (PM) in the longer anisomyopic eye (LAE) was associated with increased risk of PM in the SAE. METHODS: 1168 HMs were recruited from Singapore National Eye Centre clinic for this cross-sectional study. Biometry, fundus photography and swept-source optical coherence tomography were performed. Patients with high axial anisomyopia were identified. Structural characteristics and presence of PM were described. Stepwise multivariate regression explored associations between PM in the LAE and pathology in the SAE, controlling for confounding variables. RESULTS: Prevalence of anisomyopia was 15.8% (184 of 1168 patients). Anisomyopic patients (age 65.8±13.5 years) had mean AL of 30.6±2.0 mm and 26.2±2.3 mm in the LAE and SAE, respectively. 52.7% of SAEs had AL < 26.5 mm. Prevalence of myopic macular degeneration, macula-involving posterior staphyloma (PS), myopic traction maculopathy (MTM) and myopic choroidal neovascularisation (mCNV) in the SAE was 52.2%, 36.5%, 13.0% and 8.2%, respectively. Macular hole in the LAE was associated with increased risk of MTM in the SAE (OR=4.88, p=0.01). mCNV in the LAE was associated with mCNV in the SAE (OR=3.57, p=0.02). PS in the LAE was associated with PS in the SAE (OR=4.03, p<0.001). CONCLUSIONS: Even when controlled for AL, PM complications in the LAE predict similar PM complications in the SAE. Patients with high axial anisometropia with PM in the LAE should be monitored carefully for complications in the SAE.

SIRT6 deficiency causes ovarian hypoplasia by affecting Plod1-related collagen formation.

SIRT6 is a key member of the mammalian sirtuin family of conserved nicotinamide adenine dinucleotide (NAD+ )-dependent deacetylases. Previous studies have shown that SIRT6 can regulate metabolism, DNA damage repair and aging. Ovarian aging process usually share similar mechanisms with general aging, which is characterized by decreases in both numbers of ovarian follicles and the quality of oocytes. It is reported that the expression level of SIRT6 was significantly decreased in the ovaries of aged mice, and the level of SIRT6 was positively correlated with ovarian reserve, indicating that SIRT6 may be potential markers of ovarian aging. However, its biological roles in follicular development are still unclear. Here, we explored the effect of SIRT6 on follicular development and found that ovarian development was interrupted in SIRT6 knockout (KO) mice, leading to disruptions of puberty and the estrus cycle, significant decreases in numbers of secondary and antral follicles, and decreased collagen in the ovarian stroma. Plod1, a lysyl hydroxylase that is vital for collagen crosslinking and deposition, was decreased at both the mRNA and protein levels in SIRT6-deficient ovaries and granulosa cells (GCs). Additionally, we found abnormal estrogen levels in both SIRT6 KO mice and SIRT6 KD GCs, accompanied by decreases in the levels of the estrogen biosynthesis genes Cyp11a1, Cyp19a1, Mgarp, and increases in the levels of TNF-α and NF-κB. These results confirmed the effect of SIRT6 on follicular development and revealed a possible molecular mechanism for SIRT6 involvement in follicular development via effects on estrogen biosynthesis and collagen formation.

LLGL2 Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via ACTN1.

Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells.