Solid-state polymer-particle hybrid electrolytes: Structure and electrochemical properties.

Solid-state electrolytes (SSEs) are challenged by complex interfacial chemistry and poor ion transport through the interfaces they form with battery electrodes. Here, we investigate a class of SSE composed of micrometer-sized lithium oxide (Li2O) particles dispersed in a polymerizable 1,3-dioxolane (DOL) liquid. Ring-opening polymerization (ROP) of the DOL by Lewis acid salts inside a battery cell produces polymer-inorganic hybrid electrolytes with gradient properties on both the particle and battery cell length scales. These electrolytes sustain stable charge-discharge behavior in Li||NCM811 and anode-free Cu||NCM811 electrochemical cells. On the particle length scale, Li2O retards ROP, facilitating efficient ion transport in a fluid-like region near the particle surface. On battery cell length scales, gravity-assisted settling creates physical and electrochemical gradients in the hybrid electrolytes. By means of electrochemical and spectroscopic analyses, we find that Li2O particles participate in a reversible redox reaction that increases the effective CE in anode-free cells to values approaching 100%, enhancing battery cycle life.

Modelling, Characterization of Data-Dependent and Process-Dependent Errors in DNA Data Storage.

Using DNA as the medium to store information has recently been recognized as a promising solution for long-term data storage. While several system prototypes have been demonstrated, the error characteristics in DNA data storage are discussed with limited content. Due to the data and process variations from experiment to experiment, the error variation and its effect on data recovery remain to be uncovered. To close the gap, we systematically investigate the storage channel, i.e., error characteristics in the storage process. In this work, we first propose a new concept named sequence corruption to unify the error characteristics into the sequence level, easing the channel analysis. Then we derived the formulations of the data imperfection at the decoder including both sequence loss and sequence corruption, revealing the decoding demand and monitoring the data recovery. Furthermore, we extensively explored several data-dependent unevenness observed in the base error patterns and studied a few potential factors and their impacts on the data imperfection at the decoder both theoretically and experimentally. The results presented here introduce a more comprehensive channel model and offer a new angle towards the data recovery issue in DNA data storage by further elucidating the error characteristics of the storage process.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Modulation of rumen fermentation and microbial community through increasing dietary cation-anion difference in Chinese Holstein dairy cows under heat stress conditions.

AIMS: The effect of increasing dietary cation-anion difference (DCAD) on rumen fermentation and ruminal microbial community in dairy cows under heat stress (HS) conditions were evaluated. METHODS AND RESULTS: This study was performed as a two-period cross-over design during the summer season, with eight lactating dairy cows randomly distributed to either a control DCAD diet (CON: 33·5 mEq/100 g DM) or high DCAD diet (HDCAD: 50·8 mEq/100 g DM). Throughout the present study, the temperature and humidity index (THI; 80·2 ± 4·29) was generally elevated above the threshold (THI = 72) that is reported to cause HS in lactating dairy cows. Rumen liquid samples were collected on 15 and 21 d during each 21 d-period. The absolute concentration of ruminal total volatile fatty acid (TVFA) in HDCAD treatment was significantly (P < 0·05) higher than those in the control, whilst the ruminal pH, NH3 -N, and VFA molar percentages were unaffected through increasing DCAD. Furthermore, the copy numbers of the cellulolytic bacteria Ruminococcus albus and Ruminococcus flavefaciens in rumen fluid significantly (P < 0·05) rose along with the increment of DCAD. Although the Alpha diversity indexes and the bacterial microbiota structure were unaffected, increasing DCAD significantly (P < 0·05) enriched the phylum Fibrobacteres and genus Fibrobacter in the microflora of rumen fluid, whilst the genera Flexilinea and Dubosiella were the most differentially abundant taxa in the control. CONCLUSIONS: Increasing DCAD under HS conditions resulted in a greater concentration of total VFA without affecting rumen bacteria diversity or structure, although the enrichment of some cellulolytic/hemicellulolytic bacteria was observed. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study provides information on the modulation of rumen fermentation and microbial community through the increment of DCAD in Holstein dairy cows under HS conditions.

[Discovery and study on potential effect of herbal pair of Uncariae Ramulus cum Uncis-Eucommiae Cortex on pregnancy hypertension based on network pharmacology and molecular docking].

This study aimed to explore the optimal indications and mechanism of Uncariae Ramulus cum Uncis(UR)-Eucommiae Cortex(EC) in lowering blood pressure based on network pharmacology and molecular docking. Chemical constituents were collected and screened by TCMSP database. Swiss Target Prediction platform was used to predict the related targets of the drug. OMIM, TCMIP and GeneCards databases were used to collect hypertension-related genes, and the intersections were taken to obtain potential targets for anti-hypertensive treatment of UR-EC. FunRich software was used to enrich the clinical phenotype and expression site of potential target of lowering blood pressure to analyze and predict the optimal indications of UR-EC. STRING database was used for KEGG pathway enrichment analysis, and Cytoscape 3.7.2 was used to construct the network of "composition-target-pathway". The key targets and their corresponding components in the network were analyzed and obtained, and then molecular docking was applied for preliminary verification. Twenty potential active components of UR and 24 potential active components of EC were respectively collected, and 92 anti-hypertensive potential targets of UR-EC were obtained. According to FunRich enrichment results, the optimal indication of UR-EC was pregnancy hypertension, which involved calcium signaling pathway, HIF-1 signaling pathway, neuroactive ligand receptor interaction, renin vascular tightening, VEGF signaling pathway, etc. In addition, AKT1, NOS2, ADRB2, F2, NOS3, SCN5 A, HTR2 A and JAK2 were considered as the key targets in the network. The molecular docking results showed that the screened potential active components had high binding activity with the key targets. This study preliminarily revealed that UR-EC may have therapeutic effects on pregnancy hypertension in terms of sedation, anti-hypertension, anti-inflammatory, anti-oxidation, improvement of vascular endothelial function and so on.

[Research progress on effective components of Chinese materia medica in regulating autophagy].

Autophagy is a highly conservative and multi-component activated energy metabolism and self-renewal mechanism, which plays a crucial regulatory role in maintaining the normal physiological state of cells and is involved in various pathological processes. In recent years, the mechanism study has made great progress in regulating autophagy with effective components of Chinese materia medica(CMM),which are reported to prevent and treat cancers, neurodegenerative diseases, cardiovascular diseases and metabolic and immune-related diseases. This review outlines the molecular regulation mechanisms of cell autophagy with CMM components in controlling the above-mentioned diseases. There are many relevant reports on the regulatory mechanisms of autophagy in tumor and cardiovascular cells with CMM monomers. The main chemical structural types are alkaloids, saponins, polyphenols, flavonoids and terpenes. And m-TOR pathway is the main mechanism relating to the regulatory mechanisms of autophagy with CMM. Therefore, the regulatory mec-hanisms of cell autophagy become a new research targeting strategy of therapies with CMM. This review provides evidences for the effectiveness and scientificity of CMM in regulating autophagy, in the expectation of providing references for the in-depth studies of CMM in the field of autophagy and the development of natural autophagy regulators.

[Study on lipid production by reusing herb residues of Songling Xuemaikang Capsules].

Songling Xuemaikang Capsules is a Chinese patent medicine mainly made of the Chineses medicine Puerariae Lobatae Radix and leaves of Pinus massoniana. During its production, a large amount of herb extraction residues would be treated as wastes, resulting in resource wasting and serious environmental pollution. In order to solve this problem, we took the hydrolysates of Puerariae Lobatae Radix, P. massoniana leaves, and whole herb residues of Songling Xuemaikang Capsules as the fermentation substrate to explore the ability of Rhodosporidium toruloides to produce microbial lipid. The results showed that the R. toruloides could produce lipid with use of the residues from Songling Xuemaikang Capsules, and the lipid contents reached 33.6%. The lipid products had similar fatty acid composition profiles to those of vegetable oils. Herb residues were converted into fermentation substrates in this study, and were recycled into the production of high value-added compounds to realize the transformation of the wastes, laying the foundation for the sustainable utilization of herb residues.

Genome-wide Analyses Identify a Novel Risk Locus for Nonsyndromic Cleft Palate.

The 3 major subphenotypes observed in patients with nonsyndromic orofacial clefts (NSOFCs) are nonsyndromic cleft lip only (NSCLO), nonsyndromic cleft lip with palate (NSCLP), and nonsyndromic cleft palate only (NSCPO). However, the genetic architecture underlying NSCPO is largely unknown. Here we performed a 2-stage genome-wide association study (GWAS) on NSCPO and replication analyses of selected variants in other NSOFCs from the Chinese Han population. We identified a novel locus (15q24.3) and a known locus (1q32.2) where variants in or near the gene reached genome-wide significance (2.80 × 10-13 < P < 1.72 × 10-08) in a test for association with NSCPO in a case-control design. Although a variant from 15q24.3 was found to be significantly associated with both NSCPO and NSCLP, the direction of estimated effects on risk were opposite. Our functional annotation of the risk alleles within 15q24.3 coupled with previously established roles of the candidate genes within identified risk loci in periderm development, embryonic patterning, and/or regulation of cellular processes supports their involvement in palate development and the pathogenesis of cleft palate. Our study advances the understanding of the genetic basis of NSOFCs and provides novel insights into the pathogenesis of NSCPO.

Oligo Design with Single Primer Binding Site for High Capacity DNA-Based Data Storage.

DNA has become an attractive medium for long-term data archiving due to its extremely high storage density and longevity. Short single-stranded DNAs, called oligonucleotides (oligos), have been designed and synthesized to store digital data. Previous works designed the oligos with a pair of primer binding sites (PBSs) (each with a length of around 200) attached at the two ends of each basic readable data block. The addition of PBSs decreases the data density significantly because in the current DNA synthesis, the maximum length of a synthesized oligo in good quality is around 200. Furthermore, the maximum homopolymer run allowed by the existing experiments has been reported to be three nucleotides. In this work, to increase the data density, we have devised and tested an oligo design for DNA-based storage with the basic readable data block appended by a single PBS at one end only, while allowing the maximum homopolymer run to be increased to 4. We also present an oligo assembly algorithm that can reconstruct oligos with a single PBS from the error-prone raw readouts obtained from the sequencing process. We have conducted a wet lab experiment to validate the proposed design, where we tested with 398KB of data stored into 10,750 oligos. The experimental results show that it is possible to recover over 99 percent of the oligo sequences without error, which proves that one PBS is sufficient for implementing a DNA-based data storage system with maximum homopolymer run relaxed to 4. The use of single PBS leads to a significant data density gain from 14.3 to 140.2 percent over the existing short-strand DNA data storage schemes by reserving more nucleotides for storing information bits.

Heme oxygenase-1 attenuates the inhibitory effect of bortezomib against the APRIL-NF-κB-CCL3 signaling pathways in multiple myeloma cells: Corelated with bortezomib tolerance in multiple myeloma.

Osteoclasts (OCs) play an essential role in bone destruction in patients with multiple myeloma (MM). Bortezomib can ameliorate bone destruction in patients with MM, but advanced MM often resists bortezomib. We studied the molecular mechanisms of bortezomib tolerance in MM. The expression of the MM-related genes in newly diagnosed patients with MM and normal donors were studied. C-C motif chemokine ligand 3 (CCL3) is a cytokine involved in the differentiation of OCs, and its expression is closely related to APRIL (a proliferation-inducing ligand). We found that bortezomib treatment inhibited APRIL and CCL3. But the heme oxygenase-1 (HO-1) activator hemin attenuated the inhibitory effects of bortezomib on APRIL and CCL3. We induced mononuclear cells to differentiate into OCs, and the enzyme-linked immunosorbent assay showed that the more OCs differentiated, the higher the levels CCL3 secretions detected. Animal experiments showed that hemin promoted MM cell infiltration in mice. The weight and survival rate of tumor mice were associated with HO-1 expression. Immunohistochemical staining showed that HO-1, APRIL, and CCL3 staining were positively stained in the tumor infiltrating sites. Then, MM cells were transfected with L-HO-1/si-HO-1 expression vectors and cultured with an nuclear factor (NF)-kappa B (κB) pathway inhibitor, QNZ. The results showed that HO-1 was the upstream gene of APRIL, NF-κB, and CCL3. We showed that HO-1 could attenuate the inhibitory effect of bortezomib against the APRIL-NF-κB-CCL3 signaling pathways in MM cells, and the tolerance of MM cells to bortezomib and the promotion of bone destruction are related to HO-1.

Autologous breast reconstruction using the immediately lipofilled extended latissimus dorsi flap.

BACKGROUND: The latissimus dorsi flap is a popular choice for autologous breast reconstruction. To dramatically improve volume, we report our experience of using the immediately lipofilled extended latissimus dorsi (ELD) flap and show it as a valid option for autologous breast reconstruction. METHODS: Patients undergoing the procedure between December 2013 and June 2016 were included. Demographic, clinical and operative factors were analysed, together with in-hospital morbidity and duration of postoperative hospital stay. RESULTS: A total of 71 ELD flaps with immediate lipofilling were performed. Forty-five reconstructions were immediate and the remaining 26 delayed. Median (range) volume of autologous fat injected immediately was 171 ml (40-630 ml). Contralateral reductions were performed in 25 patients with the median reduction volume 185 g (89-683 g). Median duration of admission was 6.5 (3-18) days and patients were followed up for 12 months (1-37). Three total flap failures occurred and had to be excised (4%). One haematoma occurred requiring drainage (1%). Signs of infection requiring intravenous antibiotics occurred in five patients (7%). In 5 patients wound dehiscence occurred, and only two of these required resuturing (3%). In total, 7 patients developed a seroma requiring repeated drainage (10%). Three reconstructions experienced mild mastectomy flap necrosis with no needing reoperation (4%). CONCLUSIONS: Our experience represents the largest series to date and shows that in carefully selected patients the technique is safe, can avoid the requirement for implants, and has the potential to streamline the reconstructive journey.

[Liquid milk exposure and risk assessment of thiocyanate in Chinese populations].

Objective: To analyze liquid milk exposure of thiocyanate among Chinese population and preliminarily assess its health risk. Methods: A total of 2 059 raw milk samples were collected during 2013 and 2014 from 12 Chinese provinces, New Zealand and Netherlands. Farms were chosed according to the main sources of dairy companies, the distribution of farms and the yield of milk. Content of thiocyanate were detected by ion chromatography. Liquid milk consumption data were taken from Chinese beverage and alcoholic beverage consumption survey in 18 cities or counties in 9 provinces, including 16 775 subjects older than 3. A simple distribution model was used to estimate the exposure of thiocyanate from liquid milk. The tolerable daily intake (TDI) of thiocyanate was made 0.08 mg·kg(-1)·d(-1). Then the exposures of different age groups were compared with TDI. Results: Finally, 1 331 samples out of 2 059 were detected to contain thiocyanate. The detection rate was 65%. The average concentration of thiocyanate was 2.11 mg/kg, with a range of 0.10-16.20 mg/kg. The general population's consumption of thiocyanate by drinking liquid milk was 0.001 mg · kg(-1) · d(-1), which was lower than TDI. The P(95) of general population and consumers were 0.009 mg · kg(-1) · d(-1) and 0.020 mg·kg( -1)·d(-1) respectively, which were also lower than TDI. Mean exposures of population aged 3-6, 7-12, 13-17, 18-59 as well as elderly aged 60 and above were 0.007, 0.003, 0.002, 0.001 and 0.001 mg · kg(-1)·d(-1) respectively, which were all lower than TDI. Conclusion: The results suggested that the health risk of thiocyanate exposure by drinking liquid milk among Chinese population was at a low level. However, milk products for children deserve more concern.

The risk to the cutaneous nerve branches in the anterior (Wagner) and snuff-box approaches to the trapezium: a cadaveric study.

We compared the risk with the subcutaneous nerves with the anterior (Wagner) and snuff-box approaches to the trapezium in cadavers. Branches that crossed tattooed incision markings or lay within 1 cm of the markings were identified on six matched pairs of fresh-frozen cadaveric hands. Their distance from the proximal end of the incision was recorded. For anterior incisions, there were 20 vulnerable branches in total, at a mean distance of 22 mm from the proximal end of the incision. A total of 13 lay in the distal half of the incision. For snuff-box incisions, there were 18 vulnerable branches in total, at a mean distance of 11 mm from the proximal end of the incision, with 17 of them lying in the proximal half of the incision. Neither incision is without risk to nerve braches, but our study suggests a lesser risk of subcutaneous nerve damage with the snuff-box approach and highlights the greater risk in the proximal half of this incision.

A cadaveric study of the distribution pattern of the cutaneous sensory fibres of the distal palm of the hand.

We investigated the cutaneous innervation of the distal palm, an area frequently dissected by the hand surgeon. Ten (five paired) fresh-frozen cadaveric hands were dissected under 3.0× loupe magnification. Volar branches were found on both sides in the majority of digits. They originated alongside, or at the proximal margin of, the A1 pulley in 84% of digits. The mean distance from the palmar digital crease to the origin of volar branches was 21 mm.

Atypical focal cortical dysplasia in a patient with Cowden syndrome.

A macrocephalic girl presented with generalised epilepsy due to focal cortical dysplasia. She later developed multiple hamartomatous lesions and was diagnosed to have Cowden syndrome. The diagnosis was confirmed by identification of a novel frameshift mutation in the PTEN gene of the patient.

Efficacy of electrical stimulation for spinal fusion: a meta-analysis of fusion rate.

BACKGROUND CONTEXT: Many clinical studies have demonstrated the effectiveness of electrical stimulation as an adjunct to spinal arthrodesis. However, there is a paucity of comparative data among different electrical stimulation techniques. PURPOSE: To compare the efficacy of three electrical stimulation methods for spinal fusion based on the literature review. SAMPLE: Twenty-one articles, meeting all the inclusion criteria, were selected. A total of 1,381 patients were evaluated. STUDY DESIGN: Systematic literature review and meta-analysis. OUTCOME MEASURES: Fusion rates were determined using radiography or computed tomography. METHODS: A systematic literature review was conducted on spinal fusion surgeries with the aid of electrical stimulation devices. Only studies applying radiography or computed tomography for fusion assessment were included. Study groups were divided based on electrical stimulation types and were further grouped by other patient characteristics. Pooled estimates and 95% confidence intervals (CIs) were calculated by random-effects meta-analysis. RESULTS: The pooled fusion rate for all studies was 85% (95% CI, 79-90). There were 14 direct current, 1 capacitive coupling (CC), and 10 inductive coupling studies in our analysis, with combined fusion rate of 85% (95% CI, 76-91), 90% (95% CI, 83-95), and 85% (95% CI, 74-93), respectively. There were no statistically significant differences among the three electrical stimulation methods. Further subgroup analysis suggested that age, sex, smoking status, surgery type, fusion levels, fusion column, implant use, and graft type did not significantly influence the fusion rate. CONCLUSIONS: The three types of electrical stimulation devices had similar clinical efficacy in promoting bone growth for spinal fusion. The results for CC stimulation should be applied with caution as only one relevant study was identified.

Percutaneous anterior occiput-to-axis screw fixation: technique aspects and case series.

BACKGROUND CONTEXT: Posterior occipitocervical fusion techniques have been previously described; however, traditional open anterior approaches are plagued by exposure difficulty. A minimally invasive percutaneous anterior occipitocervical fixation approach avoids this difficult exposure procedure. PURPOSE: This article describes a novel technique of percutaneous anterior occiput-to-axis screw fixation and its clinical outcomes. STUDY DESIGN: Technique report. METHODS: Anteroposterior, lateral and open-mouth views, and computed tomography scans are preoperatively obtained to appraise the feasibility of surgery. We extend our experience of using percutaneous anterior transarticular screw fixation to occiput-to-axis screw fixation. This procedure was performed on six patients. RESULTS: The operation was successfully performed on all patients without technical difficulties, and no vertebral artery, nerve injury or soft tissue (such as esophageal) complications occurred. All six patients followed up 10 to 39 months (averaged 20.5 months). Bone union was achieved in five patients, and the one patient lacking bone union was stable at final follow-up. The syringomyelia of four patients is almost complete reduction. No screw loosening or breakage has occurred. CONCLUSIONS: With the correct puncture point, angle of insertion, and use of the appropriate tools, we suggest that percutaneous anterior occiput-to-axis fixation technique is a feasible, safe, and minimally invasive procedure.

Selective and brain-permeable polo-like kinase-2 (Plk-2) inhibitors that reduce α-synuclein phosphorylation in rat brain.

Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology. Potent, selective, brain-penetrant inhibitors of Plk-2 were obtained from a structure-guided drug discovery approach driven by the first reported Plk-2-inhibitor complexes. The best of these compounds showed excellent isoform and kinome-wide selectivity, with physicochemical properties sufficient to interrogate the role of Plk-2 inhibition in vivo. One such compound significantly decreased phosphorylation of α-synuclein in rat brain upon oral administration and represents a useful probe for future studies of this therapeutic avenue toward the potential treatment of Parkinson's disease.