Polarization self-compensation in a laser-driven interferometric fiber optic gyroscope with high long-term stability.

We present a laser-driven interferometric fiber optic gyroscope (IFOG) with polarization self-compensation to achieve high scale-factor stability, sensitivity, and long-term stability. Coherent light with 200kHz linewidth is employed to keep the scale factor stable. The optical scheme ensures polarization reciprocity as well as the optimal working point for good sensitivity. Furthermore, a hybrid machine learning loop (MLL) method, combining the advantages of PID fast response and artificial neural network (ANN) dynamic search, can control a liquid crystal rotator (LCR) to dynamically compensate for slow drift induced by polarization coupling. In open environment, when the sensitivity is 0.005 ∘/h, the bias instability (BI) is significantly optimized from 0.6723°/h at 60s (PID) to 0.3869°/h at 200s (MLL), which is close to the Sagnac interferometric limit (SIL). Such IFOG can meet the real-time and robust requirements for inertial navigation systems in long-term measurement.

Coherent feedback enhanced quantum-dense metrology in a lossy environment.

Quantum dense metrology (QDM) performs high-precision measurements by a two-mode entangled state created by an optical parametric amplifier (PA), where one mode is a meter beam and the other is a reference beam. In practical applications, the photon losses of meter beam are unavoidable, resulting in a degradation of the sensitivity. Here, we employ coherent feedback that feeds the reference beam back into the PA by a beam splitter to enhance the sensitivity in a lossy environment. The results show that the sensitivity is enhanced significantly by adjusting the splitting ratio of the beam splitter. This method may find its potential applications in QDM. Furthermore, such a strategy that two non-commuting observables are simultaneous measurements could provide a new way to individually control the noise-induced random drift in phase or amplitude of the light field, which would be significant for stabilizing the system and long-term precision measurement.

Protection of Noise Squeezing in a Quantum Interferometer with Optimal Resource Allocation.

Interferometers are crucial for precision measurements, including gravitational waves, laser ranging, radar, and imaging. The phase sensitivity, the core parameter, can be quantum-enhanced to break the standard quantum limit (SQL) using quantum states. However, quantum states are highly fragile and quickly degrade with losses. We design and demonstrate a quantum interferometer utilizing a beam splitter with a variable splitting ratio to protect the quantum resource against environmental impacts. The optimal phase sensitivity can reach the quantum Cramér-Rao bound of the system. This quantum interferometer can greatly reduce the quantum source requirements in quantum measurements. In theory, with a 66.6% loss rate, the sensitivity can break the SQL using only a 6.0 dB squeezed quantum resource with the current interferometer rather than a 24 dB squeezed quantum resource with a conventional squeezing-vacuum-injected Mach-Zehnder interferometer. In experiments, when using a 2.0 dB squeezed vacuum state, the sensitivity enhancement remains at ∼1.6 dB via optimizing the first splitting ratio when the loss rate changes from 0% to 90%, indicating that the quantum resource is excellently protected with the existence of losses in practical applications. This strategy could open a way to retain quantum advantages for quantum information processing and quantum precision measurement in lossy environments.

Binding mechanism of oseltamivir and influenza neuraminidase suggests perspectives for the design of new anti-influenza drugs.

Oseltamivir is a widely used influenza virus neuraminidase (NA) inhibitor that prevents the release of new virus particles from host cells. However, oseltamivir-resistant strains have emerged, but effective drugs against them have not yet been developed. Elucidating the binding mechanisms between NA and oseltamivir may provide valuable information for the design of new drugs against NA mutants resistant to oseltamivir. Here, we conducted large-scale (353.4 µs) free-binding molecular dynamics simulations, together with a Markov State Model and an importance-sampling algorithm, to reveal the binding process of oseltamivir and NA. Ten metastable states and five major binding pathways were identified that validated and complemented previously discovered binding pathways, including the hypothesis that oseltamivir can be transferred from the secondary sialic acid binding site to the catalytic site. The discovery of multiple new metastable states, especially the stable bound state containing a water-mediated hydrogen bond between Arg118 and oseltamivir, may provide new insights into the improvement of NA inhibitors. We anticipated the findings presented here will facilitate the development of drugs capable of combating NA mutations.

An efficient method for knocking out genes on the virulence plasmid of hypervirulent Klebsiella pneumoniae.

Currently, the infection of hypervirulent Klebsiella pneumoniae (hvKp) is becoming increasingly serious and the virulent mechanisms of hvKp are still not very clear. An effective gene-editing method for genes on hvKp virulence plasmid can help us reveal related virulent mechanisms. There are a few reports focusing on the methods mentioned above, however with certain limitations. In this work, we first constructed the pRE112-basing recombinant suicide plasmid to knock out or replace the genes in the hvKp virulence plasmid based on the principle of homology recombination. Results showed that the target virulent genes iucA, iucB, iroB, and rmpA2 on the hvKp virulence plasmid were scarlessly knocked out or replaced by marker genes, and mutant hvKp strains with the expected phenotypes were obtained. These indicated that we established an efficient gene-editing method for genes on hvKp virulence plasmid, which could help us explore the functions of these genes and reveal the virulent mechanisms of hvKp.

[Research progress on role of traditional Chinese medicine in hepatic fibrosis based on miRNA-mediated activation of NLRP3 inflammasome].

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1ß and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.

The quality of diabetes care among cancer survivors: a retrospective cohort study.

BACKGROUND: As cancer survivorship continues to improve, management of co-morbid diabetes has become an increasingly important determinant of health outcomes for people with cancer. This study aimed to compare indicators of diabetes quality of care between people with diabetes and without a history of cancer. METHODS: We used the Electronic Medical Record Administrative data Linked Database (EMRALD), a database of Ontario primary care EMR charts linked to administrative data, to identify people with diabetes and at least 1 year follow-up. Persons with a history of cancer were matched 1:2 on age, sex and diabetes duration to those without cancer. We compared recommended diabetes quality of care indicators between persons with and without cancer using a matched cohort analysis. RESULTS: Among 229,627 people with diabetes, we identified 2275 people with cancer and 4550 matched controls; 86.5% had diabetes diagnosed after cancer. Compared to controls, cancer people with diabetes were significantly less likely to receive ACE inhibitors or angiotensin receptor blockers (OR 0.75 [95% CI 0.64-0.89]), receive statin therapy if age 50-80 years (OR 0.79 [95% CI 0.68-0.92]) and achieve an LDL cholesterol level <2.0 mmol/L (OR 0.82 [95% CI 0.74-0.91]). There were no differences in recommended clinical testing or achieving A1C and blood pressure targets between groups. CONCLUSION: Cancer survivors with diabetes are less likely to receive recommended cardiovascular risk-reducing therapies compared to people with diabetes without cancer of similar age, sex and diabetes duration. Further studies are warranted to determine if these associations are linked to worse survival, cardiovascular outcomes and quality of life.

Developments in the study of gastrointestinal microbiome disorders affected by FGF19 in the occurrence and development of colorectal neoplasms.

Colorectal neoplasms are a type of malignant digestive system tumor that has become the third-highest morbidity tumor in China and the fourth leading cause of cancer-related death worldwide. The role of the gastrointestinal (GI) microbiome in bile acid metabolism, inflammation, and insulin resistance and its strong correlation with the occurrence and development of colorectal neoplasms have gradually led to it becoming a target area of tumor research. Fibroblast growth factor (FGF) 19 is a hormone that is secreted in mainly the ileum and can regulate bile acid biosynthesis, improve inflammation, and regulate insulin resistance. The relationship of the GI microbiome, FGF19 and its carcinogenic activities in colorectal neoplasms enticed us to search for potential targets and research ideas for the clinical diagnosis and treatment of colorectal neoplasms.

Chinese herbal decoction of Wenshen Yangxue formula improved fertility and pregnancy rate in mice through PI3K/Akt signaling.

OBJECTIVE: Traditional Chinese medicine (TCM) is an effective management to infertility. The association between TCM-mediated fertility and inhibition of phosphatidylinositol-3-kinase (PI3K) would be investigated. METHODS: Institute of Cancer Research mice were treated with three herbal decoctions, named Wenshen Yangxue formula, Wenshen formula, and Yangxue formula, plus with human gonadotropins. PI3K inhibitor wortmannin was administrated to half of mice. Some index such as body weight, fertility ability would be investigated. The expression of P13K/Akt signaling was detected by using Western blot analysis. RESULTS: No difference was observed in body weight among groups. Mice receiving the administration of human gonadotropins and herbal decoctions showed increased follicle numbers, percentage of fertilization, and promoted embryonic development. The treatment of Wenshen Yangxue formula decoction showed the highest efficiency, significant higher than Wenshen and Yangxue formulas. And increased the expression of p-PI3K and p-Akt proteins. CONCLUSION: These results suggested the herbal decoctions promoted the fertilization of mice, which was related to the charge of PI3K/Akt activation.

Incidence and Risk Factors for Leukopenia in Kidney Transplant Recipients Receiving Valganciclovir for Cytomegalovirus Prophylaxis.

CONTEXT: Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The epidemiology of leukopenia in patients on valganciclovir remains poorly understood. OBJECTIVE: To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation. METHODS: In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis. The Kaplan-Meier product limit method was used to graphically assess time to leukopenia, and risk factors were assessed using Cox proportional hazards models. RESULTS: A total of 542 kidney transplant recipients were included in the study cohort. The cumulative incidence of leukopenia at 6 months posttransplant was 39.3% (11.0% for neutropenia). Low baseline white blood cell count (hazard ratio [HR] 2.34 [95% confidence interval [CI], 1.37-4.00]) and high baseline body mass index (HR 1.05 [95% CI, 1.02-1.09]) were independently associated with an increased risk of leukopenia, while higher Cockcroft-Gault creatinine clearance (HR 0.87 [95% CI, 0.78-0.97]) was significantly associated with a decreased risk of leukopenia. CONCLUSIONS: These data suggest that recipient baseline white blood cell count, baseline body mass index, and kidney function are clinical predictors of new-onset leukopenia after kidney transplantation. Our results may inform the approach to cytomegalovirus prophylaxis to reduce the risk of valganciclovir-induced leukopenia in kidney transplant recipients.

[Effect of Wenshen Yangxue Recipe on Inhibin-Activin-Follistatin System in Anovulatory Rats].

Objective To explore the effect of Wenshen Yangxue Recipe (WYR) on inhibin-ac- tivin-follistatin (INH-ACT-FS) system and gonadal hormone level in anovulatory rats. Methods Anovula- tory rat model was established in 76 rats (9 days old) by subcutaneous injecting testosterone propionate (1. 25 mg/0. 05 mL for each rat) from the nape. Totally 58 successfully modeled rats were divided into 5 groups according to random digit table, i.e., the model group (n =10), the Western medicine (WM) group (n =12), high, middle, and low dose WYR groups (n =12). Besides, another ten 22-day old rats were recruited as a normal group. Distilled water was daily administered to rats in the normal group and the model group by gastrogavage. Clomiphene citrate (0. 58 mg/100 g) was daily administered to rats in the WM group for 5 successive days. WYR at 5. 2, 2. 6, 1. 3 mg/100 g was daily administered to rats in high, middle, and low dose WYR groups for 21 successive days. Levels of follicular stimulating hormone (FSH) , luteinizing hormone (LH) , estradiol (E2) , progesterone (P) , and prolactin (PRL) were detected using radioimmunoassay. Contents of inhibin (INH) , activin (ACT) , and follistatin (FS) were measured using ELISA. Results Compared with the normal group, serum levels of FSH and LH increased, and P level decreased in the model group (P <0. 05) ; INH level decreased and FS level increased in the model group (P<0. 05). Compared with the model group, serum FSH level decreased in the WM group and 3 WYR groups, P level decreased in the WM group (P <0. 05); INH increased and FS levels decreased in the WM group and 3 WYR groups; ACT level increased in the high dose WYR group, with statistical differ- ence (P <0. 05). Conclusion WYR promoted follicular development possibly through regulating INH- ACT-FS system and gonadal hormone level.

YOLO-plum: A high precision and real-time improved algorithm for plum recognition.

Real-time, rapid, accurate, and non-destructive batch testing of fruit growth state is crucial for improving economic benefits. However, for plums, environmental variability, multi-scale, occlusion, overlapping of leaves or fruits pose significant challenges to accurate and complete labeling using mainstream algorithms like YOLOv5. In this study, we established the first artificial dataset of plums and used deep learning to improve target detection. Our improved YOLOv5 algorithm achieved more accurate and rapid batch identification of immature plums, resulting in improved quality and economic benefits. The YOLOv5-plum algorithm showed 91.65% recognition accuracy for immature plums after our algorithmic improvements. Currently, the YOLOv5-plum algorithm has demonstrated significant advantages in detecting unripe plums and can potentially be applied to other unripe fruits in the future.

Association Between Maternal Glucose Levels in Gestational Diabetes Screening and Subsequent Hypertension.

BACKGROUND: We assessed the association between maternal glucose levels in pregnancy and subsequent hypertension. METHODS: This population-level, retrospective cohort study examined women aged 12 to 54 years with singleton pregnancies completed at ≥29 weeks of gestation from October 1, 2008 to December 1, 2018 followed until March 31, 2019 in Alberta, Canada. Women were stratified by results in the 50-gram glucose challenge test and by 75-gram oral glucose tolerance test subtypes (normal oral glucose tolerance test, elevated fasting plasma glucose only [elevated fasting], elevated postload glucose only, or both elevated fasting and postload glucose [combined]. Time to development of hypertension was modeled using Cox proportional hazards models. RESULTS: Of 313 361 women, 231 008 (79.1%) underwent a glucose challenge test only while 60 909 (20.9%) underwent either an oral glucose tolerance test only or both. Nine thousand five hundred eighty (3.1%) developed hypertension, and 2824 (0.9%) developed cardiovascular disease over a median follow-up of 5.7 years. Every 1-mmol/L increase in glucose in the glucose challenge test increased the risk of subsequent hypertension by 15% (adjusted hazard ratio and 95% CI, 1.15 [1.14-1.16]). Among those who underwent the oral glucose tolerance test, the combined group conferred the highest risk of subsequent hypertension, followed by elevated fasting, then elevated postload glucose only (reference: glucose challenge test ≤7.1 mmol/L, adjusted hazard ratio [95% CI]: elevated postload glucose only, 1.83 [1.68-2.00]; elevated fasting 2.02 [1.70-2.40]; combined, 2.65 [2.33-3.01]). No significant associations between maternal glucose levels and cardiovascular disease were observed. CONCLUSIONS: Increasing maternal glucose levels in pregnancy were associated with increasing risk of subsequent hypertension. These findings may help identify higher-risk women who should be targeted for earlier postpartum cardiovascular risk reduction.

The Avoiding Diabetes After Pregnancy Trial in Moms Program: Feasibility of a Diabetes Prevention Program for Women With Recent Gestational Diabetes Mellitus.

OBJECTIVE: Our aim in this study was to evaluate the feasibility of a home-based diabetes prevention program, delivered by interdisciplinary certified diabetes educators (CDEs), and customized for postpartum women with recent gestational diabetes mellitus (GDM). METHODS: This pilot randomized trial recruited women with GDM from 24 to 40 weeks gestation from 4 centres, and trained 10 CDEs in behaviour coaching, physical activity (PA) and low glycemic index education. Women were randomized after 3 months postpartum to standard care (1 visit) or 1 of 3 24-week coaching interventions (1 visit and 12 telephone calls): i) PA and diet, ii) PA only or iii) diet only. Feasibility outcomes included recruitment, retention, adherence and satisfaction. RESULTS: Of 1,342 eligible patients, 392 were actively invited (29.3%) and 227 (16.9%) consented. Of these, 149 (65.6%) were randomized postpartum, of whom 131 (87.9%) started the program and 105 (70.5%) attended the final assessment. Intervention arm participants completed a median 75% (interquartile range, 50% to 92%) of telephone calls. Visit and call duration were a mean 71.4 (standard deviation, 13.8) and 18.1 (standard deviation, 6.5) minutes, respectively. Participants reported excellent/very good satisfaction 73% of the time, and 87% would recommend the program to others. CONCLUSIONS: A home-based diabetes prevention program customized for postpartum women with GDM can be feasibly delivered by CDEs, and it is associated with >70% retention, adherence and satisfaction.

Serum biomarker analysis in patients with recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) occurs in 1­5% of parturients. The sustained therapy and research for RSA is expensive, which is a serious issue faced by both patients and doctors. The aim of the present study was to detect protein expression profiles in the serum of RSA patients and healthy controls, and to identify potential biomarkers for this disease. A 1,000­protein microarray consisting of a combination of Human L­507 and L­493 was used. The microarray data revealed that eight serum protein expression levels were significantly upregulated and 143 proteins were downregulated in RSA patients compared with the healthy controls. ELISA individually validated 5 of these 151 proteins in a larger cohort of patients and control samples, demonstrating a significant decrease in insulin­like growth factor­binding protein­related protein 1 (IFGBP­rp1)/IGFBP­7, Dickkopf­related protein 3 (Dkk3), receptor for advanced glycation end products (RAGE) and angiopoietin­2 levels in patients with RSA. Sensitivity and specificity analyses were calculated by a receiver operating characteristics curve, and were revealed to be 0.881, 0.823, 0.79 and 0.814, with diagnostic cut­off points of 95.44 ng/ml for IFGBP­rp1, 32.84 ng/ml for Dkk3, 147.27 ng/ml for RAGE and 441.40 ng/ml for angiopoietin­2. The present study indicated that these four proteins were downregulated in RSA samples and may be useful as biomarkers for the prediction and diagnosis of RSA. Subsequent studies in larger­scale cohorts are required to further validate the diagnostic value of these markers.

Intra-islet glucagon secretion and action in the regulation of glucose homeostasis.

Glucagon, a key hormone in the regulation of glucose homeostasis, acts as a counter-regulatory hormone to insulin by promoting hepatic glucose output. Under normal conditions, insulin and glucagon operate in concert to maintain the glucose level within a narrow physiological range. In diabetes, however, while insulin secretion or action is insufficient, the production and secretion of glucagon are excessive, contributing to the development of diabetic hyperglycemia. Within an islet, intra-islet insulin, in cooperation with intra-islet GABA, suppresses glucagon secretion via direct modulation of α-cell intracellular signaling pathways involving Akt activation, GABA receptor phosphorylation and the receptor plasma membrane translocation, while intra-islet glucagon plays an important role in modulating ß-cell function and insulin secretion. Defects in the insulin-glucagon fine-tuning machinery may result in ß-cell glucose incompetence, leading to unsuppressed glucagon secretion and subsequent hyperglycemia, which often occur under extreme conditions of glucose influx or efflux. Therefore, deciphering the precise molecular mechanisms underlying glucagon secretion and action will facilitate our understanding of glucagon physiology, in particular, its role in regulating islet ß-cell function, and hence the mechanisms behind glucose homeostasis.

Regulation and control of wenshen yangxue granule combined with clomifene citrate on INH-ACT-FS system in patients with follicular maldevelopment infertility / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical curative effect of Wenshen Yangxue Granule (WSYXG) combined with clomifene citrate (CC) in treating follicular maldevelopment (FM) infertility, and to explore its possible action channels.</p><p><b>METHODS</b>Ninety patients with FM of Shen-deficiency blood stasis syndrome were randomly assigned to 3 groups, i.e., the Chinese medicine group (CMG, treated with WXYXG), the Western medicine group (WMG, treated with CC), and the combination group of Chinese medicine and Western medicine (CG, treated with both WSYXG and CC), 30 cases in each group. Three menstrual cycles were totally observed. Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2 ), inhibin B (INHB), activin A (ACTA), and follistatin (FS) were tested before and after treatment, and the ovulation was monitored and their basic body temperature measured.</p><p><b>RESULTS</b>There was no statistical difference in clinical efficacy among the three groups (P> 0.05). Better effects on the Chinese medicine syndrome efficacy, the ovulation rate, and the endometrium thickness on the ovulation day were shown in CMG and CG than in WMG, showing statistical difference (P < 0.05). The E2 level increased on the third day of the first menstrual cycle in CG when compared with before treatment. On the 10th day of the 1st menstrual cycle, the INHB and FS increased and the ACTA decreased, showing statistical difference (P < 0.05). On the 10th day of the 3rd menstrual cycle the serum LH level decreased more obviously in CG than in WMG, showing statistical difference (P < 0.05). On the 3rd day of the 3rd menstrual cycle in CG, the INHB was negatively correlated with FSH (r = -0.492,P < 0.01), and INHB on the 10th day was positively correlated with E2 and FS (r = 0.682, 0.772, P < 0.01), and negatively correlated with ACTA on the 10th day (r = -0.635, P < 0.01).</p><p><b>CONCLUSION</b>WSYXG combined with CC could improve Chinese medicine syndrome, regulate the expressions of FM patients' ovary local factors INHB, ACTA and FS, improve the condition of ovary functions, and control the follicle development.</p>