Bowel Habits, Obesity, Intestinal Microbiota and Their Influence on Hemorrhoidal Disease: a Mendelian Randomization Study.

Purpose: Hemorrhoids (HEM) are the most common perianal disease, but current observational studies have yielded inconsistent results in investigating the risk factors. Our further exploration of the risk factors will help prevent the disease. Patients and Methods: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics from multiple consortia. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and Cochrane's Q value, to detect and correct the effects of horizontal pleiotropy. Results: Genetically determined constipation (OR = 0.97, 95% CI: 0.91-1.03, P = 0.28) and diarrhea (OR = 1.00, 95% CI: 0.99-1.01, P = 0.90) did not have a causal effect on HEM but stool frequency (OR = 1.28, 95% CI: 1.05-1.55, P = 0.01), waist-to-hip ratio adjusted for BMI (OR = 1.11, 95% CI: 1.06-1.64, P = 1.59×10-5), and order Burkholderiales (OR = 1.09, 95% CI = 1.04-1.14, p = 1.63×10-4) had a causal effect on. Furthermore, we found a significant causal effect of constipation on HEM in the reverse MR analysis (OR = 1.21, 95% CI: 1.13-1.28, P = 3.72×10-9). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates, as indicated by the sensitivity analysis. Conclusion: Our MR analysis reveals a causal association between stool frequency and waist-to-hip ratio with HEM, despite variations in results reported by observational studies. Unexpectedly, we found a relationship between the order Burkholderiales in the gut flora and HEM, although the mechanism is unclear.

Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

Highly Potent and Low-Volume Concentration Additives for Durable Aqueous Zinc Batteries: Machine Learning-Enabled Performance Rationalization.

The essential virtues of aqueous zinc battery chemistry stem from the energy-dense zinc metal anode and mild aqueous electrolytes. Yet, their incompatibility - as exposed by zinc's corrosion and associated dendrite problem - poses a challenge to achieving improved cycle life under practically relevant parameters. While electrolyte additives are a scalable strategy, additives that can function at low volume concentrations remain elusive. Here, through screening alkanol and alkanediol chemistries, 1,2-butanediol and pentanediol are unveiled as highly potent additives, which operate at a practical 1 volume% concentration owing to their ability to furnish dynamic solid-electrolyte interphase through pronounced interfacial filming. This unique mechanistic action renders effective corrosion and dendrite mitigation, resulting in up to five to twenty-fold zinc cyclability enhancement with a high Coulombic efficiency (up to 99.9%) and improved full-cell performance under demanding conditions, including at elevated temperatures. A machine learning-based analysis is presented to rationalize the additive performance relative to critical physicochemical descriptors, which can pave the way for a rational approach to efficient additive discoveries.

Breast cancer therapies reduce risk of Alzheimer's disease and promote estrogenic pathways and action in brain.

Worldwide, an ever-increasing number of women are prescribed estrogen-modulating therapies (EMTs) for the treatment of breast cancer. In parallel, aging of the global population of women will contribute to risk of both breast cancer and Alzheimer's disease. To address the impact of anti-estrogen therapies on risk of Alzheimer's and neural function, we conducted medical informatic and molecular pharmacology analyses to determine the impact of EMTs on risk of Alzheimer's followed by determination of EMT estrogenic mechanisms of action in neurons. Collectively, these data provide both clinical and mechanistic data indicating that select EMTs exert estrogenic agonist action in neural tissue that are associated with reduced risk of Alzheimer's disease while simultaneously acting as effective estrogen receptor antagonists in breast.

Mixed-Valence CuI /CuIII Metal-Organic Frameworks with Non-innocent Ligand for Multielectron Transfer.

We report two novel three-dimensional copper-benzoquinoid metal-organic frameworks (MOFs), [Cu4 L3 ]n and [Cu4 L3 ⋅ Cu(iq)3 ]n (LH4 =1,4-dicyano-2,3,5,6-tetrahydroxybenzene, iq=isoquinoline). Spectroscopic techniques and computational studies reveal the unprecedented mixed valency in MOFs, formal Cu(I)/Cu(III). This is the first time that formally Cu(III) species are witnessed in metal-organic extended solids. The coordination between the mixed-valence metal and redox-non-innocent ligand L, which promotes through-bond charge transfer between Cu metal sites, allows better metal-ligand orbital overlap of the d-π conjugation, leading to strong long-range delocalization and semiconducting behavior. Our findings highlight the significance of the unique mixed valency between formal Cu(I) and highly-covalent Cu(III), non-innocent ligand, and pore environments of these bench stable Cu(III)-containing frameworks on multielectron transfer and electrochemical properties.

Phosphorylation-dependent recognition of diverse protein targets by the cryptic GK domain of MAGI MAGUKs.

Dynamic signal transduction requires the rapid assembly and disassembly of signaling complexes, often mediated by phosphoprotein binding modules. The guanylate kinase-like (GK) domain of the membrane-associated guanylate kinases (MAGUKs) is such a module orchestrating signaling at cellular junctions. The MAGI subfamily of MAGUKs contains a truncated GK domain with unknown structure and function, although they participate in diverse physiological and pathological processes. Here, we demonstrate that the truncated GK domain of MAGI2 interacts with its adjacent PDZ0 domain to form a structural supramodule capable of recognizing phosphoproteins. A conserved phosphorylation-dependent binding motif for PDZ0-GK is delineated, which leads to identification of a set of previously unknown binding partners. We explore the structure and function of the MAGI2-target complex with an inhibitory peptide derived from the consensus motif. Our work reveals an action mechanism of the cryptic MAGI GKs and broadens our understanding of the target recognition rules of phosphoprotein binding modules.

Anthocyanins from Malus spp. inhibit the activity of Gymnosporangium yamadae by downregulating the expression of WSC, RLM1, and PMA1.

Malus plants are frequently devastated by the apple rust caused by Gymnosporangium yamadae Miyabe. When rust occurs, most Malus spp. and cultivars produce yellow spots, which are more severe, whereas a few cultivars accumulate anthocyanins around rust spots, forming red spots that inhibit the expansion of the affected area and might confer rust resistance. Inoculation experiments showed that Malus spp. with red spots had a significantly lower rust severity. Compared with M. micromalus, M. 'Profusion', with red spots, accumulated more anthocyanins. Anthocyanins exhibited concentration-dependent antifungal activity against G. yamadae by inhibiting teliospores germination. Morphological observations and the leakage of teliospores intracellular contents evidenced that anthocyanins destroyed cell integrity. Transcriptome data of anthocyanins-treated teliospores showed that differentially expressed genes were enriched in cell wall and membrane metabolism-related pathways. Obvious cell atrophy in periodical cells and aeciospores was observed at the rust spots of M. 'Profusion'. Moreover, WSC, RLM1, and PMA1 in the cell wall and membrane metabolic pathways were progressively downregulated with increasing anthocyanins content, both in the in vitro treatment and in Malus spp. Our results suggest that anthocyanins play an anti-rust role by downregulating the expression of WSC, RLM1, and PMA1 to destroy the cell integrity of G. yamadae.

Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration.

Astrocytes provide key neuronal support, and their phenotypic transformation is implicated in neurodegenerative diseases. Metabolically, astrocytes possess low mitochondrial oxidative phosphorylation (OxPhos) activity, but its pathophysiological role in neurodegeneration remains unclear. Here, we show that the brain critically depends on astrocytic OxPhos to degrade fatty acids (FAs) and maintain lipid homeostasis. Aberrant astrocytic OxPhos induces lipid droplet (LD) accumulation followed by neurodegeneration that recapitulates key features of Alzheimer's disease (AD), including synaptic loss, neuroinflammation, demyelination and cognitive impairment. Mechanistically, when FA load overwhelms astrocytic OxPhos capacity, elevated acetyl-CoA levels induce astrocyte reactivity by enhancing STAT3 acetylation and activation. Intercellularly, lipid-laden reactive astrocytes stimulate neuronal FA oxidation and oxidative stress, activate microglia through IL-3 signalling, and inhibit the biosynthesis of FAs and phospholipids required for myelin replenishment. Along with LD accumulation and impaired FA degradation manifested in an AD mouse model, we reveal a lipid-centric, AD-resembling mechanism by which astrocytic mitochondrial dysfunction progressively induces neuroinflammation and neurodegeneration.

A Molecular Engineering Strategy for Achieving Blue Phosphorescent Carbon Dots with Outstanding Efficiency above 50.

Highly efficient emission has been a long-lasting pursuit for carbon dots (CDs) owing to their enormous potential in optoelectronic applications. Nevertheless, their room-temperature phosphorescence (RTP) performance still largely lags behind their outstanding fluorescence emission, especially in the blue spectral region. Herein, high-efficiency blue RTP CDs have been designed and constructed via a simple molecular engineering strategy, enabling CDs with an unprecedented phosphorescence quantum efficiency of to 50.17% and a long lifetime of 2.03 s. This treating route facilitates the formation of high-density (n, π*) configurations in the CD π-π conjugate system through the introduction of abundant functional groups, which can evoke a strong spin-orbit coupling and further promote the intersystem crossing from singlet to triplet excited states and radiative recombination from triplet excited states to ground state. With blue phosphorescent CDs as triplet donors, green, red, and white afterglow composites are successfully fabricated via effective phosphorescence Förster resonance energy transfer. Importantly, the color temperature of the white afterglow emission can be widely and facilely tuned from cool white to pure white and warm white. Moreover, advanced information encryption, light illumination, and afterglow/dynamic visual display have been demonstrated when using these multicolor-emitting CD-based afterglow systems.

Allopregnanolone pleiotropic action in neurons and astrocytes: calcium signaling as a unifying mechanism.

Objective: Allopregnanolone (Allo) is a neurosteroid with pleiotropic action in the brain that includes neurogenesis, oligogenesis, human and rodent neural stem cell regeneration, increased glucose metabolism, mitochondrial respiration and biogenesis, improved cognitive function, and reduction of both inflammation and Alzheimer's disease (AD) pathology. Because the breadth of Allo-induced responses requires activation of multiple systems of biology in the absence of an Allo-specific nuclear receptor, analyses were conducted in both neurons and astrocytes to identify unifying systems and signaling pathways. Methods: Mechanisms of Allo action were investigated in embryonic hippocampal neurons and astrocytes cultured in an Aging Model (AM) media. Cellular morphology, mitochondrial function, and transcriptomics were investigated followed by mechanistic pathway analyses. Results: In hippocampal neurons, Allo significantly increased neurite outgrowth and synaptic protein expression, which were paralleled by upregulated synaptogenesis and long-term potentiation gene expression profiles. Mechanistically, Allo induced Ca2+/CREB signaling cascades. In parallel, Allo significantly increased maximal mitochondrial respiration, mitochondrial membrane potential, and Complex IV activity while reducing oxidative stress, which required both the GABAA and L-type Ca2+ channels. In astrocytes, Allo increased ATP generation, mitochondrial function and dynamics while reducing oxidative stress, inflammasome indicators, and apoptotic signaling. Mechanistically, Allo regulation of astrocytic mitochondrial function required both the GABAA and L-type Ca2+ channels. Furthermore, Allo activated NRF1-TFAM signaling and increased the DRP1/OPA1 protein ratio, which led to increased mitochondrial biogenesis and dynamics. Conclusion: Collectively, the cellular, mitochondrial, transcriptional, and pharmacological profiles provide evidence in support of calcium signaling as a unifying mechanism for Allo pleiotropic actions in the brain.

Malnutrition and infection lead to poor prognosis and heavy financial burden of patients with chronic heart failure.

Background: Chronic heart failure (CHF) is a major public health concern, as it is associated with poor prognosis and heavy financial burden. In recent years, there has been increasing interest in medications for CHF in China, but few studies pay attention to the effects of nutrition and infection. Methods and results: This was a retrospective study collected patients with CHF admitted to the Department of Cardiology of Qilu Hospital of Shandong University from January 2017 to May 2018. Patients were classified according to the prognosis and the financial burden. Through comparison and regression analysis, we found that the factor associated with worse prognosis were decreased heart rate, albumin and prealbumin; ß-blockers and mineralocorticoid receptor antagonism (MRA) were the factor improved the prognosis of patients with CHF; the factor overburdening financial condition were infection, decreased prealbumin, high Alanine aminotransferase (ALT), usage of recombinant human brain natriuretic peptide (rhBNP) and Levosimendan; aspirin and Sacubitril/Valsartan were the factor releasing financial burden of patients with CHF. Then, we grouped by Controlling Nutritional Status (CONUT) score, which enabled evaluation of the patient's protein reserve and immune defenses. Patients in the malnutrition group had higher infection ratios, longer hospital stays, and greater hospital expenses than the normal group. The improvement ratios of therapeutic outcomes in the moderate or severe malnutrition group were lower than in the normal and mild malnutrition group. Conclusion: Malnutrition and infection caused poor prognosis and increased financial burden of patients with CHF. The high CONUT score indicated the CHF patient's unfavorable prognosis and heavy financial burden.

Effect of the Replacement of Maize Silage and Soyabean Meal with Mulberry Silage in the Diet of Hu Lambs on Growth Performance, Serum Biochemical Indices, Slaughter Performance, and Meat Quality.

Maize silage has a high demand for fertilizer and water. As an unconventional feed resource, mulberry silage has the potential to replace most maize silage and to alleviate the shortage of roughage in the mutton sheep industry in China. The purpose of this experiment was to study the effect of the replacement of maize silage and soyabean meal with mulberry silage in the diet of Hu lambs on growth performance, serum biochemical indices, slaughter performance, and meat quality. Ninety-six healthy Hu lambs were randomly divided into four groups with six replicates per group and four lambs per replicate. The amounts of 0, 20, 40, and 60% of maize silage were replaced by mulberry silage in each group (denoted as CON, L, M, and H, respectively). The results showed that replacing maize silage with mulberry silage had no significant effect on the growth performance or the slaughter performance of Hu lambs (p > 0.05). Feeding Hu lambs with mulberry silage significantly reduced serum glucose (GLU) and the blood urea nitrogen (BUN) content (p < 0.05), and it increased the content of ether extract (EE) in the longissimus dorsi muscle (p < 0.05). Meanwhile, the percentage of EAA in the M and H groups was significantly lower than that in the CON and L groups (p < 0.05). In addition, in the fatty acid profile, the percentage of C16:1 in the M group was significantly increased, while the percentage of C18:0 and C20:0 were significantly decreased (p < 0.05). Based on these findings, it was recommended that 20−40% of maize silage be replaced by mulberry silage in the diet of Hu lambs.

3D Printing Nanostructured Solid Polymer Electrolytes with High Modulus and Conductivity.

The development of advanced solid-state energy-storage devices is contingent upon finding new ways to produce and manufacture scalable, high-modulus solid-state electrolytes that can simultaneously provide high ionic conductivity and robust mechanical integrity. In this work, an efficient one-step process to manufacture solid polymer electrolytes composed of nanoscale ion-conducting channels embedded in a rigid crosslinked polymer matrix via Digital Light Processing 3D printing is reported. A visible-light-mediated polymerization-induced microphase-separation approach is utilized, which produces materials with two chemically independent nanoscale domains with highly tunable nanoarchitectures. By producing materials containing a poly(ethylene oxide) domain swelled with an ionic liquid, robust solid polymer electrolytes with outstanding room-temperature (22 °C) shear modulus (G' > 108 Pa) and ionic conductivities up to σ = 3 × 10-4 S cm-1 are achieved. The nanostructured 3D-printed electrolytes are fabricated into a custom geometry and employed in a symmetric carbon supercapacitor, demonstrating the scalability of the fabrication and the functionality of the electrolyte. Critically, these high-performance materials are manufactured on demand using inexpensive and commercially available 3D printers, which allows the facile modular design of solid polymer electrolytes with custom geometries.

Replacement of Maize Silage and Soyabean Meal with Mulberry Silage in the Diet of Hu Lambs on Growth, Gastrointestinal Tissue Morphology, Rumen Fermentation Parameters and Microbial Diversity.

Maize silage has a significant environmental impact on livestock due to its high requirement for fertilizer and water. Mulberry has the potential to replace much of the large amount of maize silage grown in China, but its feeding value in the conserved form needs to be evaluated. We fed Hu lambs diets with 20-60% of the maize silage replaced by mulberry silage, adjusting the soybean meal content when increasing the mulberry silage inclusion rate in an attempt to balance the crude protein content of the diets. Mulberry silage had higher crude protein and lower acidic and neutral detergent fiber contents compared to maize silage. Replacing maize silage and soyabean meal with mulberry silage had no effect on the feed intake and growth rate of Hu lambs. However, the rumen pH increased, the acetate to propionate in rumen fluid increased, and the rumen ammonia concentration decreased as mulberry replaced maize silage and soyabean meal. This was associated with an increase in norank_f__F082 bacteria in the rumen. Rumen papillae were shorter when mulberry silage replaced maize silage, which may reflect the reduced neutral detergent fiber (NDF) content of the original silage. In conclusion, mulberry silage can successfully replace maize silage and soyabeans in the diet of Hu lambs without loss of production potential, which could have significant environmental benefits.

The Prognostic Value of Sarcopenia and Myosteatosis in Biliary Tract Cancer After Palliative Treatment With Radiation-Emitting Metallic Stent.

Background: Radiation-emitting metallic stent (REMS) placement is increasingly used for malignant biliary obstruction (MBO) caused by unresectable biliary tract carcinoma (UBTC) in clinical practice. The study is aimed to evaluate the prognostic value of sarcopenia, myosteatosis, and their combination on overall survival (OS) in patients treated with REMS for UBTC. Methods: Patients diagnosed with UBTC who underwent REMS placement between January 2013 and May 2021 were included consecutively in this retrospective study. Sarcopenia and myosteatosis were defined based on skeletal muscle index (SMI) and skeletal muscle attenuation (SMA), respectively, which were measured by computer tomography (CT) images on the level of the third lumbar vertebral body before REMS placement. Patients were categorized into two groups by sex-specific cutoff value for sarcopenia and myosteatosis, and OS rates were compared between the groups. Univariate and multivariate cox regression analyses were used to assess factors associated with OS. Results: Data of 135 patients included were retrospectively reviewed and analyzed. Median OS was 7.17 months in total cohort. Patients in the sarcopenia group had significant poorer OS than those in the non-sarcopenia group (median: 3.23 vs. 11.60 months, p < 0.001). OS was shorter in patients with myosteatosis than those without myosteatosis (median: 4.40 vs. 9.17 months, p < 0.001). Sarcopenia (odds ratio [OR] = 9.61; 95% CI = 5.41-17.09; p < 0.001) and myosteatosis (OR = 1.70; 95% CI = 1.13-2.57; p = 0.012) were significantly associated with OS. Combining sarcopenia and myosteatosis (CSM) showed a better predictive accuracy in OS than either one (area under curves: CSM vs. sarcopenia = 0.760 vs. 0.698, p = 0.049; CSM vs. myosteatosis = 0.760 vs. 0.671, p = 0.006). Conclusion: Sarcopenia and myosteatosis are negative predictors of survival in patients who underwent REMS placement for UBTC. CSM seemed to show a better prognostic value than either sarcopenia or myosteatosis alone. They can be used preoperatively for risk evaluation.

CIDEC: A Potential Factor in Diabetic Vascular Inflammation.

Cell death-inducing DFF45-like effector C (CIDEC) is involved in diet-induced adipose inflammation. Whether CIDEC plays a role in diabetic vascular inflammation remains unclear. A type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated its characteristics by metabolic tests, Western blot analysis of CIDEC and C1q/tumor necrosis factor-related protein-3 (CTRP3) expression, and histopathological analysis of aortic tissues. The diabetic group exhibited elevated CIDEC expression, aortic inflammation, and remodeling. To further investigate the role of CIDEC in the pathogenesis of aortic inflammation, gene silencing was used. With CIDEC gene silencing, CTRP3 expression was restored, accompanied with amelioration of insulin resistance, aortic inflammation, and remodeling in diabetic rats. Thus, the silencing of CIDEC is potent in mediating the reversal of aortic inflammation and remodeling, indicating that CIDEC may be a potential therapeutic target for vascular complications in diabetes.

PGF2α-FP Receptor Ameliorates Senescence of VSMCs in Vascular Remodeling by Src/PAI-1 Signal Pathway.

Senescence in vascular smooth muscle cells (VSMCs) is involved in vascular remodeling of aged mice. ProstaglandinF2α- (PGF2α-) FP receptor plays a critical role in cardiovascular diseases (CVDs), hypertension, and cardiac fibrosis. However, its role in senescence-induced arteriosclerosis is yet to be fully elucidated. In this study, we found that FP receptor expression increased in aged mouse aortas and senescence VSMCs. FP receptor gene silencing can ameliorate vascular aging and inhibit oxidative stress, thereby reducing the expression of PAI-1, inhibiting the activation of MMPs, and ultimately improving the excessive deposition of ECM and delaying the process of vascular fibrosis. FP receptor could promote VSMC senescence by upregulated Src/PAI-1 signal pathway, and inhibited FP receptor/Src/PAI-1 pathway could ameliorate VSMCs aging in vitro, evidenced by the decrease of senescence-related proteins P16, P21, P53, and GLB1 expressions. These results suggested that FP receptor is a promoter of vascular aging, by inducing cellular aging, oxidative stress, and vascular remodeling via Src and PAI-1 upregulation.

Entropy of stapled peptide inhibitors in free state is the major contributor to the improvement of binding affinity with the GK domain.

Stapled peptides are promising protein-protein interaction (PPI) inhibitors that can increase the binding potency. Different from small-molecule inhibitors in which the binding mainly depends on energetic interactions with their protein targets, the binding of stapled peptides has long been suggested to be benefited from entropy. However, it remains challenging to reveal the molecular features that lead to this entropy gain, which could originate from the stabilization of the stapled peptide in solution or from the increased flexibility of the complex upon binding. This hinders the rational design of stapled peptides as PPI inhibitors. Using the guanylate kinase (GK) domain of the postsynaptic density protein 95 (PSD-95) as the target, we quantified the enthalpic and entropic contributions by combining isothermal titration calorimetry (ITC), X-ray crystallography, and free energy calculations based on all-atom molecular dynamics (MD) simulations. We successfully designed a stapled peptide inhibitor (staple 1) of the PSD-95 GK domain that led to a 25-fold increase in the binding affinity (from tens of µMs to 1.36 µM) with high cell permeability. We showed that entropy indeed greatly enhanced the binding affinity and the entropy gain was mainly due to the constrained-helix structure of the stapled peptide in solution (free state). Based on staple 1, we further designed two other stapled peptides (staple 2 and 3), which exerted even larger entropy gains compared to staple 1 because of their more flexible bound complexes (bound state). However, for staple 2 and 3, the overall binding affinities were not improved, as the loose binding in their bound states led to an enthalpic loss that largely compensated the excess entropy gain. Our work suggests that increasing the stability of the stapled peptide in free solution is an effective strategy for the rational design of stapled peptides as PPI inhibitors.

Adjuvant Radiotherapy After Minimally Invasive Surgery in Patients With Stage IA1-IIA1 Cervical Cancer.

To estimate whether adjuvant radiotherapy is necessary for patients with stage IA1-IIA1 cervical cancer after laparoscopic hysterectomy, 221 patients were retrospectively analyzed. Sixty-two of them were treated with laparoscopic hysterectomy and adjuvant radiotherapy (group A), 115 underwent open surgery (group B) and 44 received laparoscopic hysterectomy alone (group C). Results showed that the 3-year local recurrence-free survival (LRFS) rates of group A, B and C were 98.4%, 97.4% and 86.4%, respectively. The LRFS rates of group A and B surpassed C (A vs. B, p=0.634; A vs. C, p=0.011; B vs. C, p=0.006). The inter-group differences of 3-year overall survival (OS) and distant metastasis free survival (DMFS) were not statistically significant. In subgroup analysis of stage IB disease, the 3-year LRFS rates of group A, B and C were 100%, 98.8% and 83.1%, the 3-year OS rates of group A, B and C were 100%, 98.9% and 91.5%, respectively. The 3-year LRFS and OS rates of group A and B were significantly superior to group C (p<0.05). Our findings suggest that adjuvant radiotherapy can reduce the risk of recurrence for women with early-stage cervical cancer after laparoscopic hysterectomy and bring survival benefits for patients with stage IB disease.