Preserving frozen stallion sperm on dry ice using polymers that modulate ice crystalization kinetics.

Cryopreserved semen is routinely shipped in liquid nitrogen. Dry ice could serve as an alternative coolant, however, frozen storage above liquid nitrogen temperatures (LN2, -196 °C) may negatively affect shelf-life and cryosurvival. In this study, we determined critical temperatures for storage of cryopreserved stallion sperm. We evaluated: (i) effects of cooling samples to different subzero temperatures (-10 °C to -80 °C) prior to storing in LN2, (ii) stability at different storage temperatures (i.e., in LN2, dry ice, -80 °C and -20 °C freezers, 5 °C refrigerator), and (iii) sperm cryosurvival during storage on dry ice (i.e., when kept below -70 °C and during warming). Furthermore, (iv) we analyzed if addition of synthetic polymers (PVP-40, Ficoll-70) modulates ice crystallization kinetics and improves stability of cryopreserved specimens. Sperm motility and membrane intactness were taken as measures of cryosurvival, and an artificial insemination trial was performed to confirm fertilizing capacity. We found that adding PVP-40 or Ficoll-70 to formulations containing glycerol reduced ice crystal sizes and growth during annealing. Post-thaw sperm viability data indicated that samples need to be cooled below -40 °C before they can be safely plunged and stored in LN2. No negative effects of relocating specimens from dry ice to LN2 and vice versa became apparent. However, sample warming above -50 °C during transport in dry ice should be avoided to ensure preservation of viability and fertility. Moreover, addition of PVP-40 or Ficoll-70 was found to increase sperm cryosurvival, especially under non-ideal storage conditions where ice recrystallization may occur.

Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study.

OBJECTIVES: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl-1/mIU∙l-1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). METHODS: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl-1/mIU∙l-1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. RESULTS: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. CONCLUSIONS: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl-1/mIU∙l-1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03224312).

Genome-Wide Identification, Expression Analysis under Abiotic Stress and Co-Expression Analysis of MATE Gene Family in Torreya grandis.

The multidrug and toxin efflux (MATE) family participates in numerous biological processes and plays important roles in abiotic stress responses. However, information about the MATE family genes in Torreya grandis remains unclear. In this study, our genome-wide investigation identified ninety MATE genes in Torreya grandis, which were divided into five evolutionary clades. TgMATE family members are located on eleven chromosomes, and a total of thirty TgMATEs exist in tandem duplication. The promoter analysis showed that most TgMATEs contain the cis-regulatory elements associated with stress and hormonal responses. In addition, we discovered that most TgMATE genes responded to abiotic stresses (aluminum, drought, high temperatures, and low temperatures). Weighted correlation network analysis showed that 147 candidate transcription factor genes regulated the expression of 14 TgMATE genes, and it was verified through a double-luciferase assay. Overall, our findings offer valuable information for the characterization of the TgMATE gene mechanism in responding to abiotic stress and exhibit promising prospects for the stress tolerance breeding of Torreya grandis.

Graphene Oxide-Enhanced and Dynamically Crosslinked Bio-Elastomer for Poly(lactic acid) Modification.

Being a bio-sourced and biodegradable polymer, polylactic acid (PLA) has been considered as one of the most promising substitutes for petroleum-based plastics. However, its wide application is greatly limited by its very poor ductility, which has driven PLA-toughening modifications to be a topic of increasing research interest in the past decade. Toughening enhancement is achieved often at the cost of a large sacrifice in strength, with the toughness-strength trade-off having remained as one of the main bottlenecks of PLA modification. In the present study, a bio-elastomeric material of epoxidized soybean oil (ESO) crosslinked with sebacic acid (SA) and enhanced by graphene oxide (GO) nanoparticles (NPs) was employed to toughen PLA with the purpose of simultaneously preserving strength and achieving additional functions. The even dispersion of GO NPs in ESO was aided by ultrasonication and guaranteed during the following ESO-SA crosslinking with GO participating in the carboxyl-epoxy reaction with both ESO and SA, resulting in a nanoparticle-enhanced and dynamically crosslinked elastomer (GESO) via a ß-hydroxy ester. GESO was then melt-blended with PLA, with the interfacial reaction between ESO and PLA offering good compatibility. The blend morphology, and thermal and mechanical properties, etc., were evaluated and GESO was found to significantly toughen PLA while preserving its strength, with the GO loading optimized at ~0.67 wt%, which gave an elongation at break of ~274.5% and impact strength of ~10.2 kJ/m2, being 31 times and 2.5 times higher than pure PLA, respectively. Moreover, thanks to the presence of dynamic crosslinks and GO NPs, the PLA-GESO blends exhibited excellent shape memory effect and antistatic properties.

Mechanochemical Release of Fluorophores from a "Flex-activated" Mechanophore.

Optical force probes that can release force-dependent and visualized signals with minimal changes in the polymer main chains under mechanical load are highly sought after but currently limited. In this study, we introduce a flex-activated mechanophore (FA) based on the Diels-Alder adduct of anthracene and dimethyl acetylenedicarboxylatea that exhibits turn-on mechanofluorescence. We demonstrate that when FA is incorporated into polymer networks or in its crystalline state, it can release fluorescent anthracenes through a retro-Diels-Alder mechanochemical reaction under compression or hydrostatic high pressure, respectively. The flex-activated mechanism of FA is successfully confirmed. Furthermore, we systematically modulate the force delivered to the mechanophore by varying the crosslinking density of the networks and the applied macroscopic pressures. This modulation leads to incremental increases in mechanophore activation, successive release of anthracenes, and quantitative enhancement of fluorescence intensity. The exceptional potential of FA as a sensitive force probe in different bulk states is highlighted, benefiting from its unique flex-activated mode with highly emissive fluorophore releasing. Overall, this report enriches our understanding of the structures and functions of flex-activated mechanophores and polymeric materials.

Group-2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2-Neutrophil-Induced Immunosuppression.

BACKGROUND AND AIMS: Due to their inherent characteristics, the function of group-2 innate lymphoid cells (ILC2s) varies in a context-dependent manner. ILC2s are involved in certain liver diseases; however, their involvement in HCC is unknown. In the present study, we assessed the role of an HCC-derived ILC2 population in tumor progression. APPROACH AND RESULTS: Through FACS and single-cell RNA sequencing, we discovered that ILC2s were highly enriched in human HCC and correlated significantly with tumor recurrence and worse progression-free survival as well as overall survival in patients. Mass cytometry identified a subset of HCC-derived ILC2s that had lost the expression of killer cell lectin-like receptor subfamily G, member 1 (KLRG1). Distinct from their circulating counterparts, these hepatic ILC2s highly expressed CD69 and an array of tissue resident-related genes. Furthermore, reduction of E-cadherin in tumor cells caused the loss of KLRG1 expression in ILC2s, leading to their increased proliferation and subsequent accumulation in HCC sites. The KLRG1- ILC2 subset showed elevated production of chemotaxis factors, including C-X-C motif chemokine (C-X-C motif) ligand (CXCL)-2 and CXCL8, which in turn recruited neutrophils to form an immunosuppressive microenvironment, leading to tumor progression. Accordingly, restoring KLRG1 in ILC2s, inhibiting CXCL2 in ILC2s, or depleting neutrophils inhibited tumor progression in a murine HCC model. CONCLUSIONS: We identified HCC-associated ILC2s as an immune regulatory cell type that promotes tumor development, suggesting that targeting these ILC2s might lead to new treatments for HCC.

Fabrication and Decryption of a Microarray of Digital Dithiosuccinimide Oligomers.

Digital polymers with precisely arranged binary units provide an important option for information storage. This is especially true if the digital polymers are assembled in a device, as it would be of great benefit for data writing and reading in practice. Herein, inspired by the DNA microarray technique, the programmable information storing and reading on a mass spectrometry target plate is proposed. First, an array of 4-bit sequence-coded dithiosuccinimide oligomers is efficiently built through sequential thiol-maleimide Michael couplings with good sequence readability by tandem mass spectrometry (MS/MS). Then, toward engineering microarrays for information storage, a programmed robotic arm is specifically designed for precisely loading sequence-coded oligomers onto the target plate, and a decoding software is developed for efficient readout of the data from MS/MS sequencing. Notably, short sequence-coded oligomer chains can be used to write long strings of information, and extra error-correction codes are not required as usual due to the inherent concomitant fragmentation signals. Not only text but also bitimages can be automatically stored and decoded with excellent accuracy. This work provides a promising platform of digital polymers for programmable information storing and reading.

EnSite NavX mapping system guided implantation of a dual-chamber permanent pacemaker in a 41-year-old pregnant woman with a 4-year follow-up.

BACKGROUND: X-ray fluoroscopy has been the primary cardiac imaging modality in permanent pacemaker implantation (PPI) operations, but it inevitably results in radiation exposure for both operators and patients. Fluoroscopy is considered a contraindication, especially in certain circumstances, such as gestation, during which the fetus is most sensitive to radiation exposure. Therefore, measures to avoid radiation exposure are necessary, and a more safe and feasible approach is needed for this procedure. Since the EnSite NavX mapping system (ENMS) can create the required geometric contours of those relevant cardiac structures and chambers, it can be used as an alternative to X-ray fluoroscopy in PPI. In addition, because the displacement of atrial leads is a common complication of PPI, lead displacement may occur more readily without fluoroscopic guidance. Therefore, reliable measures are required to prevent leads from displacement. CASE INTRODUCTION: A 41-year-old woman at the 15th week of gestation was referred to our department with recurrent episodes of syncope and amaurosis fugax for 2 years. Holter monitoring showed sinus rhythm, Mobitz Type II atrioventricular block and high-grade atrioventricular block with ventricular arrest up to 4945 ms. A dual-chamber PPI was performed successfully for the patient under the guidance of the ENMS instead of fluoroscopy. Displacement of atrial lead was effectively avoided by bending the top of atrial lead before implantation and making it a U-shape during operation, which left space for possible subsequent external pulling stress. CONCLUSIONS: For PPI, ENMS is a feasible and reliable alternative to traditional X-ray fluoroscopy, especially when performing operations on pregnant patients. By bending the top of the active-fixation atrial lead into a U-shape during operation, the displacement of atrial lead may be avoided.

Mechanochemical Release of N-Heterocyclic Carbenes from Flex-Activated Mechanophores.

We have discovered a new flex-activated mechanophore that releases an N-heterocyclic carbene (NHC) under mechanical load. The mechanophore design is based upon NHC-carbodiimide (NHC-CDI) adducts and demonstrates an important first step toward flex-activated designs capable of further downstream reactivities. Since the flex-activation is non-destructive to the main polymer chains, the material can be subjected to multiple compression cycles to achieve iterative increases in the activation percentage of mechanophores. Two different NHC structures were demonstrated, signifying the potential modularity of the mechanophore design.

TMEM88 modulates the secretion of inflammatory factors by regulating YAP signaling pathway in alcoholic liver disease.

OBJECTIVE: Transmembrane protein 88 (TMEM88), a new protein of increasing concern existed in cell membrane, inhibits the typical Wnt/ß-catenin signaling pathway to play a regulatory role on cell proliferation by binding to Dishevelled-1. Until recently, the connection between TMEM88 and alcoholic liver disease is unknown. In this research, we explored the effect of TMEM88 on the secretion of inflammatory cytokines in ethanol (EtOH)-induced RAW264.7 cells, moreover, the function of YAP signaling pathway in EtOH-induced RAW264.7 cells were investigated. METHODS: We administered TMEM88 adenovirus (ADV-TMEM88) by tail vein injection into C57BL/6J mice in vivo. In vitro, RAW264.7 murine macrophages were stimulated with EtOH and were transfected with pEGFP-C1-TMEM88 and TMEM88 siRNA, respectively, protein expression and mRNA expression of IL-6 and IL-1ß were assessed by Western Blotting and RT-qPCR, respectively. RESULTS: Our group found that the overexpression of TMEM88 led to an up-regulation of IL-6 and IL-1ß secretion, hinting that it had the possibility of linking with the initiation, the development, and the end of inflammation. In addition to that, TMEM88 silencing reduced the secretion of IL-6 and IL-1ß in RAW264.7 cells. Moreover, we demonstrated that the YAP signaling pathway under the action of EtOH was activated by TMEM88. CONCLUSIONS: All in all, these experimental outcomes indicated that TMEM88 had an indispensable impact on EtOH-induced secretion of inflammatory cytokines (IL-6 and IL-1ß) in RAW264.7 cells through YAP signaling pathway.

Downward cross-modal plasticity in single-sided deafness.

The auditory cortex has been shown to participate in visual processing in individuals with complete auditory deprivation. However, it remains unclear whether partial hearing deprivation like single-sided deafness (SSD) leads to similar cross-modal plasticity. To investigate this, we enrolled individuals with long-term SSD, into functional MRI scans under resting-state and a visuo-spatial working memory task. Contrary to previous findings in bilateral deafness, our study revealed decreased activation in the auditory cortex in both left (LSSD) and right (RSSD) single-sided deafness compared to normal hearing controls, with statistical significance in RSSD. The degree of involvement was correlated with residual hearing ability in RSSD. These observations suggest that SSD can lead to a downward cross-modal plasticity: the more hearing ability lost, the fewer brain resources in the auditory cortex can be applied to visual tasks. In addition, the fronto-parietal cortex was observed to be less activated during the visual task in RSSD while the resting-state fMRI revealed increased functional connectivity between the fronto-parietal cortex and the auditory cortex, suggesting fronto-parietal resources may be recruited less by vision but more by hearing. The LSSD showed a similar alteration trend with RSSD, but without statistical significance. Together these findings may indicate that when hearing is partially deprived in SSD, there may be redistribution for brain resources between hearing and vision, and vision tends to allocate less resources. Our findings in this pilot study of unilateral auditory-deprived individuals enrich the understanding of cross-modal plasticity in the brain.

Energy-Level Jumping Algorithm for Global Optimization in Compressive Sensing-Based Target Localization.

Target localization is one of the essential tasks in almost applications of wireless sensor networks. Some traditional compressed sensing (CS)-based target localization methods may achieve low-precision target localization because of using locally optimal sparse solutions. Solving global optimization for the sparse recovery problem remains a challenge in CS-based target localization. In this paper, we propose a novel energy-level jumping algorithm to address this problem, which achieves high-precision target localization by solving the globally optimal sparse solution of l p -norm ( 0 < p < 1 ) minimization. By repeating the process of energy-level jumping, our proposed algorithm establishes a global convergence path from an initial point to the global minimizer. Compared with existing CS-based target localization methods, the simulation results show that our localization algorithm obtain more accurate locations of targets with the significantly reduced number of measurements.

CDCS: Cluster-Based Distributed Compressed Sensing to Facilitate QoS Routing in Cognitive Video Sensor Networks.

Compressed sensing based in-network compression methods which minimize data redundancy are critical to cognitive video sensor networks. However, most existing methods require a large number of sensors for each measurement, resulting in significant performance degradation in energy efficiency and quality-of-service satisfaction. In this paper, a cluster-based distributed compressed sensing scheme working together with a quality-of-service aware routing framework is proposed to deliver visual information in cognitive video sensor networks efficiently. First, the correlation among adjacent video sensors determines the member nodes that participate in a cluster. On this basis, a sequential compressed sensing approach is applied to determine whether enough measurements are obtained to limit the reconstruction error between decoded signals and original signals under a specified reconstruction threshold. The goal is to maximize the removal of unnecessary traffic without sacrificing video quality. Lastly, the compressed data is transmitted via a distributed spectrum-aware quality-of-service routing scheme, with an objective of minimizing energy consumption subject to delay and reliability constraints. Simulation results demonstrate that the proposed approach can achieve energy-efficient data delivery and reconstruction accuracy of visual information compared with existing quality-of-service routing schemes.

[Wernicke's Encephalopathy Onset during Diagnosis and Treatment of Peritoneal Mesothelioma:Report of One Case and Literature Review].

Wernicke's encephalopathy(WE),characterized by nystagmus and ophthalmoplegia,unsteadiness of stance and gait and mental-status changes,is an acute or subacute metabolic encephalopathy of the central nervous system resulting from Vitamin B1(VitB1)deficiency. A 29-year-old male patient was admitted to our hospital due to abdominal pain and fever. He remained chronically undernourished. He was complicated with WE at the late stage of diagnosis,mainly manifested as the convulsion of limbs,ataxia,and delirium. After treatment with VitB1,these neuropsychiatric symptoms were remarkably resolved. His primary disease was later pathologically confirmed as peritoneal mesothelioma.

BF3-Promoted, Carbene-like, C-H Insertion Reactions of Benzynes.

Boron trifluoride is observed to promote a variety of C-H insertion reactions of benzynes bearing pendant alkyl groups. Computations and various mechanistic studies indicate that BF3 engages the strained π-bond to confer carbene-like character on the adjacent, noncoordinated benzyne carbon. This represents an unprecedented catalytic role for a non-transition metal such as BF3.

Identification of ERAD components essential for dislocation of the null Hong Kong variant of α-1-antitrypsin (NHK).

Misfolded proteins or orphan subunits of protein complexes are removed from the endoplasmic reticulum (ER) by ER-associated degradation (ERAD). ERAD requires dislocation, also known as retrotranslocation, of those unwanted proteins from the ER lumen to the cytosol for destruction by the proteasomes. Over one hundred ERAD component proteins have been identified but their role in dislocation remain poorly understood. Here we assessed the requirement of ERAD components for dislocation of NHK in live cells using our recently developed dislocation-induced reconstituted GFP (drGFP) assay. RNAi revealed that 12 out of 21 ERAD components examined are required for efficient dislocation of NHK among which Hrd1, Sel1L, GRP94 and p97/VCP are critically required. In addition, knockdown of 7 of the 21 components enhanced NHK dislocation. This study uncovers a complex functional network of proteins required for NHK dislocation.

Umpolung Strategy for Synthesis of ß-Ketonitriles through Hypervalent Iodine-Promoted Cyanation of Silyl Enol Ethers.

An efficient method to synthesize ß-ketonitriles from silyl enol ethers by an umploung hypervalent iodine(III)-CN species generated in situ from PhIO/BF3·Et2O/TMSCN has been developed for the first time. This method can be applied to structurally diverse aromatic and aliphatic substrates and further extended to preparation of bioactive compounds like 5-aminopyrazole and 5-aminoisoxazole.

A study of cochlear and auditory pathways in patients with tension-type headache.

BACKGROUND: The purpose of this study was to systematically evaluate the function of cochlear and auditory pathways in patients suffering from tension-type headache (TTH) using various audiological methods. METHODS: Twenty-three TTH patients (46 ears) and 26 healthy controls (52 ears) were included, and routine diagnostic audiometry, extended high-frequency audiometry, acoustic reflex (ASR), transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs) and suppression TEOAEs were tested. RESULTS: The TTH group showed higher thresholds (P < 0.05) for both pure tone and extended high-frequency audiometry at all frequencies except for 9, 14 and 16 kHz. All ASR thresholds were significantly higher (P < 0.05) in the TTH group compared with the controls, except for the ipsilateral reflex at 1 kHz, but the threshold differences between the ASR and the corresponding pure tone audiometry did not differ (P > 0.05). For the DPOAEs, the detected rates were lower (P < 0.05) in the TTH group compared with the controls at 4 and 6 kHz, and the amplitudes and signal to noise ratio (S/N) were not significantly different between groups. No differences in the TEOAEs (P > 0.05) were observed for the detected rates, amplitudes, S/Ns or contralateral suppression, except for the S/Ns of the 0.5-1 kHz TEOAE responses, which were significantly higher (P < 0.05) in the TTH group. CONCLUSIONS: The results of our study indicate that subclinical changes in cochlear function are associated with TTH.

Structural evolution during inverse vulcanization.

Inverse vulcanization exploits S8 to synthesize polysulfides. However, evolution of products and its mechanism during inverse vulcanization remains elusive. Herein, inverse vulcanization curves are obtained to describe the inverse vulcanization process in terms of three stages: induction, curing and over-cure. The typical curves exhibit a moduli increment before declining or plateauing, reflecting the process of polysulfide network formation and loosing depending on monomers. For aromatic alkenes, in the over-cure, the crosslinked polysulfide evolves significantly into a sparse network with accelerated relaxation, due to the degradation of alkenyl moieties into thiocarbonyls. The inverse vulcanization product of olefins degrades slowly with fluctuated relaxation time and modulus because of the generation of thiophene moieties, while the inverse vulcanization curve of dicyclopentadiene has a plateau following curing stage. Confirmed by calculations, the mechanisms reveal the alkenyl groups react spontaneously into thiocarbonyls or thiophenes via similar sulfur-substituted alkenyl intermediates but with different energy barriers.

IFNα-induced BST2+ tumor-associated macrophages facilitate immunosuppression and tumor growth in pancreatic cancer by ERK-CXCL7 signaling.

Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.