Unlocking Li superionic conductivity in face-centred cubic oxides via face-sharing configurations.

Oxides with a face-centred cubic (fcc) anion sublattice are generally not considered as solid-state electrolytes as the structural framework is thought to be unfavourable for lithium (Li) superionic conduction. Here we demonstrate Li superionic conductivity in fcc-type oxides in which face-sharing Li configurations have been created through cation over-stoichiometry in rocksalt-type lattices via excess Li. We find that the face-sharing Li configurations create a novel spinel with unconventional stoichiometry and raise the energy of Li, thereby promoting fast Li-ion conduction. The over-stoichiometric Li-In-Sn-O compound exhibits a total Li superionic conductivity of 3.38 × 10-4 S cm-1 at room temperature with a low migration barrier of 255 meV. Our work unlocks the potential of designing Li superionic conductors in a prototypical structural framework with vast chemical flexibility, providing fertile ground for discovering new solid-state electrolytes.

Genetically Encoded Photocaged Proteinogenic and Non-Proteinogenic Amino Acids.

Photocaged amino acids could be genetically encoded into proteins via genetic code expansion (GCE) and constitute unique tools for innovative protein engineering. There are a number of photocaged proteinogenic amino acids that allow strategic conversion of proteins into their photocaged variants, thus enabling spatiotemporal and non-invasive regulation of protein functions using light. Meanwhile, there are a hand of photocaged non-proteinogenic amino acids that address the challenges in directly encoding certain non-canonical amino acids (ncAAs) that structurally resemble proteinogenic ones or possess highly reactive functional groups. Herein, we would like to summarize the efforts in encoding photocaged proteinogenic and non-proteinogenic amino acids, hoping to draw more attention to this fruitful and exciting scientific campaign.

High toxin concentration in pollen may deter collection by bees in butterfly-pollinated Rhododendron molle.

BACKGROUNDS AND AIMS: The hypothesis that plants evolve features that protect accessible pollen from consumption by flower visitors remains poorly understood. METHODS: To explore potential chemical defenses against pollen consumption, we examined the pollinator assemblage, foraging behaviour, visitation frequency and pollen transfer efficiency in Rhododendron molle, a highly toxic shrub containing Rhodojaponin III. Nutrient (protein and lipid) and toxic components in pollen and other tissues were measured. KEY RESULTS: Overall in the five populations, floral visits by butterflies and bumblebees were relatively more frequent than visits by honeybees. All foraged for nectar but not pollen. Butterflies did not differ from bumblebees in the amount of pollen removed per visit, but deposited more pollen per visit. Pollination experiments indicated that R. molle was self-compatible, but both fruit and seed production were pollen limited. Our analysis indicated that the pollen was not protein-poor and had a higher concentration of the toxic compound Rhodojaponin III than petals and leaves, which compound was undetectable in nectar. CONCLUSION: Pollen toxicity in Rhododendron flowers may discourage pollen robbers (bees) from taking the freely accessible pollen grains, while the toxin-free nectar rewards effective pollinators, promoting pollen transfer. This preliminary study supports the hypothesis that chemical defense in pollen would be likely to evolve in species without physical protection from pollinivores.

[Application of the cigarette purchase tasks in achieving China' s tobacco control goals].

OBJECTIVE: To assess cigarette demand among Chinese smokers through a cigarette purchase task (CPT) and to evaluate cigarette prices under different hypothetical scenarios in order to meet the goals of smoking prevalence reduction in China. METHODS: In the study, 447 participants completed a hypothetical CPT at baseline assessments of a trial, thus, cigarette demand curves were individually fitted for each participant using an exponentiated version of the exponential demand model. Typically, five demand indices were derived, intensity (consumption when free), breakpoint (first price at which consumption is suppressed to 0), maximum output (Omax), maximum price (Pmax, price at which Omax occurred), and elasticity (the ratio of the change in quantity demanded to the change in price). A one-way analysis of variance was used to explore the correlations between the cigarette purchase task indices and socio-demographic and smoking characteristics. The one-way decay model was employed to simulate the smoking cessation rates and determine optimal cigarette prices in a series of scenarios for achieving 20% smoking prevalence. RESULTS: The price elasticity drawn from CPT was 0.54, indicating that a 10% price increase could reduce smoking by 5.4% in the participated smokers. Smokers with higher income were less sensitive to cigarette prices (elasticity=-2.31, P=0.028). Cigarette purchase task indices varied significantly among the smokers with different prices of commonly used cigarettes, tobacco dependence, and smoking volume. The smokers who consumed cigarettes of higher prices reported higher breakpoint, Omax and Pmax, but lower intensity (P=0.001). The smokers who were moderately or highly nicotine dependent reported higher intensity, breakpoint, Omax and Pmax, and they had lower intensity (P=0.001). The smokers who had a higher volume of cigarettes reported higher intensity and Omax, and lower intensity (P < 0.001). To achieve the goal of reducing smoking prevalence to 20% in mainland China, we estimated the desired increase on smoking cessation rate and prices accordingly in a series of scenarios, considering the gender variance and reduced smoking initiation. In scenario (a), to achieve a smoking prevalence goal of 20%, it would be necessary for 24.81% of the current smokers to quit smoking when there were no new smokers. Our fitting model yielded a corresponding value of 59.64 yuan (95%CI 53.13-67.24). Given the assumption in scenario (b) that only males quitted smoking, the desired cessation rates would be 25.82%, with a higher corresponding price of 62.15 yuan (95%CI 55.40-70.06) to induce desired cessation rates. In the proposed scenario (c) where 40 percent of the reduction in smoking prevalence came from reduced smoking initiation, and females and males equally quitted smoking due to increased cigarette prices, the price of a pack of cigarettes would be at least 37.36 yuan (95%CI 32.32-42.69) (equals to $ 5.20) per pack to achieve the cessation rate of 14.89 percent. In scenario (d) where only males quitted smoking due to increased cigarette prices considering the reduced smoking initiation, the respective smoking cessation rates should be 15.49% with the desired prices of 38.60 yuan (95%CI 33.53-44.02). After adjusting for education levels and income levels in scenario (c), the price of cigarettes would be at least 37.37 yuan/pack (equals to $ 5.20) (95%CI 30.73-44.94) and 37.84 yuan/pack (equals to $ 5.26) (95%CI 31.94-44.53), respectively. CONCLUSION: Cigarette purchase task indices are significantly associated with income levels and prices of commonly used cigarettes, levels of tobacco dependence, and smoking volume, which is inspiring in studying price factors that influence smoking behavior. It is suggested that higher cigarette prices, surpassing the current actual market level, is imperative in mainland China. Stronger policy stra-tegies should be taken to increase tobacco taxes and retail cigarette prices to achieve the Healthy China 2030 goal of reducing smoking prevalence to 20%.

Assessment of the observation management of sialocele after partial superficial parotidectomy.

PURPOSE: This study aimed to investigate the usefulness of management of sialocele formation and to evaluate the quality of life of patients under elective management post-parotidectomy. MATERIALS AND METHODS: A prospective study was performed including patients who underwent postoperative management with either compression therapy or observation. The self-filled questionnaire method was used to assess the quality of life of participants who changed from compression therapy to observation. Demographic and operative data, variables regarding wound complications and scores for quality of life were documented and analysed. RESULTS: A total of 86 patients met the eligibility criteria. The respective rates of sialocele formation within 1 month were 5.3% in the compression therapy group (2/38) and 16.0% in the observation group (4/25), but no significant difference was observed (p = 0.204). Meanwhile, both groups displayed comparable times of needle aspiration and time for sialocele resolution (p > 0.05). Based on 23 valid paired questionnaires, scores for physical and social-emotional function before changing from compression therapy to observation were significantly lower than scores after the change (p < 0.001). CONCLUSION: The application of observation after partial superficial parotidectomy appears to have acceptable clinical outcomes and considerable improvements in quality of life.

Constructing Photoactivatable Protein with Genetically Encoded Photocaged Glutamic Acid.

Genetically replacing an essential residue with the corresponding photocaged analogues via genetic code expansion (GCE) constitutes a useful and unique strategy to directly and effectively generate photoactivatable proteins. However, the application of this strategy is severely hampered by the limited number of encoded photocaged proteinogenic amino acids. Herein, we report the genetic incorporation of photocaged glutamic acid analogues in E. coli and mammalian cells and demonstrate their use in constructing photoactivatable variants of various fluorescent proteins and SpyCatcher. We believe genetically encoded photocaged Glu would significantly promote the design and application of photoactivatable proteins in many areas.

Bioconjugation via Hetero-Selective Clamping of Two Different Amines with ortho-Phthalaldehyde.

Amino groups are common in both natural and synthetic compounds and offer a very attractive class of endogenous handles for bioconjugation. However, the ability to differentiate two types of amino groups and join them with high hetero-selectivity and efficiency in a complex setting remains elusive. Herein, we report a new method for bioconjugation via one-pot chemoselective clamping of two different amine nucleophiles using a simple ortho-phthalaldehyde (OPA) reagent. Various α-amino acids, aryl amines, and secondary amines can be crosslinked to the ϵ-amino side chain of lysine on peptides or proteins with high efficiency and hetero-selectivity. This method offers a simple and powerful means to crosslink small molecule drugs, imaging probes, peptides, proteins, carbohydrates, and even virus particles without any pre-functionalization.

Expanding the Scope of Genetically Encoded Lysine Post-Translational Modifications with Lactylation, ß-Hydroxybutyrylation and Lipoylation.

Post-translational modifications (PTMs) occurring on lysine residues, especially diverse forms of acylations, have seen rapid growth over the past two decades. Among them, lactylation and ß-hydroxybutyrylation of lysine side-chains are newly identified histone marks and their implications in physiology and diseases have aroused broad research interest. Meanwhile, lysine lipoylation is highly conserved in diverse organisms and well known for its pivotal role in central metabolic pathways. Recent findings in the proteomic profiling of protein lipoylation have nonetheless suggested a pressing need for an extensive investigation. For both basic and applied research, it is necessary to prepare PTM-bearing proteins particularly in a site-specific manner. Herein, we use genetic code expansion to site-specifically generate these lysine PTMs, including lactylation, ß-hydroxybutyrylation and lipoylation in proteins in E. coli and mammalian cells. Notably, using strategies including activity-based selection, screening and rational design, unique pyrrolysyl-tRNA synthetase variants were successfully evolved for each of the three non-canonical amino acids, which enabled efficient production of recombinant proteins. Through encoding these ncAAs, we examined the deacylase activities of mammalian sirtuins to these modifications, and importantly we unfold the lipoamidase activity of several sirtuins.

Overexpression of trans-Golgi network t-SNAREs rescues vacuolar trafficking and TGN morphology defects in a putative tethering factor mutant.

The trans-Golgi network (TGN) is a major site for sorting of cargo to either the vacuole or apoplast. The TGN-localized coiled-coil protein TNO1 is a putative tethering factor that interacts with the TGN t-SNARE SYP41 and is required for correct localization of the SYP61 t-SNARE. An Arabidopsis thaliana tno1 mutant is hypersensitive to salt stress and partially mislocalizes vacuolar proteins to the apoplast, indicating a role in vacuolar trafficking. Here, we show that overexpression of SYP41 or SYP61 significantly increases SYP41-SYP61 complex formation in a tno1 mutant, and rescues the salt sensitivity and defective vacuolar trafficking of the tno1 mutant. The TGN is disrupted and vesicle budding from Golgi cisternae is reduced in the tno1 mutant, and these defects are also rescued by overexpression of SYP41 or SYP61. Our results suggest that the trafficking and Golgi morphology defects caused by loss of TNO1 can be rescued by increasing SYP41-SYP61 t-SNARE complex formation, implicating TNO1 as a tethering factor mediating efficient vesicle fusion at the TGN.

Investigation of the relationship between adhesion force and mechanical behavior of vertically aligned carbon nanotube arrays.

The mechanical behavior of vertically aligned carbon nanotube (VACNT) arrays can largely impact their adhesion performance. In this paper, we fabricated various VACNT arrays to investigate the relationship between adhesion force and their mechanical behavior. High-volume fraction (3.4%) CNT arrays did not exhibit the applicable adhesion effect due to their intrinsic elastic property. Adhesion measurements on several low-density (less than 0.5%) VACNT arrays demonstrated that the adhesion performance is strongly related to the plastic deformation of the carbon nanotubes at the contact surface. Due to the nature of the growth of CNT arrays, the top region of the as-grown CNT arrays is denser and stiffer than the bottom region of the arrays. Therefore, compared with as-grown CNT arrays, the flipped CNT arrays reached higher adhesion efficiency (the ratio of adhesion force to preload) with lower preload due to the higher compliance at the top surface of the arrays. With cyclic loading under micro mechanical tests, stiffening of the surface and declining of adhesion force were also observed. These results illustrated that the mechanical compliance at the region near the contact interface is the dominant factor for the adhesion performance of VACNT arrays.

Efficacy and safety of Chinese herbal medicine for patients with postmenopausal hypertension: A systematic review and meta-analysis.

Chinese herbal medicine has been increasingly used for patients with postmenopausal hypertension in China. A comprehensive literature search was performed in 7 electronic databases from their inception up to December 17, 2017 to examine the efficacy and safety of Chinese herbal medicine for postmenopausal hypertension. Thirty-nine randomized controlled trials involving 3, 823 participants were included. Meta-analyses favored Chinese herbal medicine plus antihypertensive drugs on blood pressure, blood pressure variability, postmenopausal symptoms, quality of life, and hormone levels compared with antihypertensive drugs. No severe adverse effects were identified. Er-xian decoction was the most frequently prescribed herbal formula, while Rehmannia glutinosa Libosch. was the most commonly used single herb. Chinese herbal medicine as complementary therapy maybe beneficial for postmenopausal hypertension. However, the effectiveness and safety of the decoction are still uncertain due to methodological shortcomings. Well-conducted trials are warranted to resolve the issue.

Reconstruction of Anterior Mandible and Mouth Floor Using the Myofascial Iliac Crest Free Flap After Tumor Resection.

The current study introduces a novel approach of anterior mandible and mouth floor reconstruction with the myofascial iliac crest free flap. A series of 4 patients who presented between May 2015 and July 2017 had benefited from this technique. The myofascial component of this flap was designed to be attached to the iliac crest, and the flap was obtained after identifying the neurovascular pedicle. We transferred the iliac crest, with an outward-oriented placement, to the mandibular defect as the base of the alveolar process. We found that the iliac crest can provide sufficient bone height and an aesthetic shape for the reconstruction of the anterior mandible. More important, we also observed that the myofascial component on the flap surface completely replaced the oral mucosa in as early as 1 month after the operation. Moreover, the proper soft tissue volume can be achieved using this approach for better functional reconstruction of the oral mucosa. No obvious scar contracture of the myofascial component was observed during the follow-up period. The myofascial iliac crest free flap could provide a suitable reconstruction method for combined oral mucosa-mandible defects.

Activation of autophagy by unfolded proteins during endoplasmic reticulum stress.

Endoplasmic reticulum stress is defined as the accumulation of unfolded proteins in the endoplasmic reticulum, and is caused by conditions such as heat or agents that cause endoplasmic reticulum stress, including tunicamycin and dithiothreitol. Autophagy, a major pathway for degradation of macromolecules in the vacuole, is activated by these stress agents in a manner dependent on inositol-requiring enzyme 1b (IRE1b), and delivers endoplasmic reticulum fragments to the vacuole for degradation. In this study, we examined the mechanism for activation of autophagy during endoplasmic reticulum stress in Arabidopsis thaliana. The chemical chaperones sodium 4-phenylbutyrate and tauroursodeoxycholic acid were found to reduce tunicamycin- or dithiothreitol-induced autophagy, but not autophagy caused by unrelated stresses. Similarly, over-expression of BINDING IMMUNOGLOBULIN PROTEIN (BIP), encoding a heat shock protein 70 (HSP70) molecular chaperone, reduced autophagy. Autophagy activated by heat stress was also found to be partially dependent on IRE1b and to be inhibited by sodium 4-phenylbutyrate, suggesting that heat-induced autophagy is due to accumulation of unfolded proteins in the endoplasmic reticulum. Expression in Arabidopsis of the misfolded protein mimics zeolin or a mutated form of carboxypeptidase Y (CPY*) also induced autophagy in an IRE1b-dependent manner. Moreover, zeolin and CPY* partially co-localized with the autophagic body marker GFP-ATG8e, indicating delivery to the vacuole by autophagy. We conclude that accumulation of unfolded proteins in the endoplasmic reticulum is a trigger for autophagy under conditions that cause endoplasmic reticulum stress.

Genome-wide mapping of transcription start sites yields novel insights into the primary transcriptome of Pseudomonas putida.

The environmental bacterium Pseudomonas putida is an organism endowed with a versatile metabolism and stress tolerance traits that are desirable in an efficient production organism. In this work, differential RNA sequencing was used to investigate the primary transcriptome and RNA regulatory elements of P. putida strain KT2440. A total of 7937 putative transcription start sites (TSSs) were identified, where over two-thirds were located either on the opposite strand or internal to annotated genes. For TSSs associated with mRNAs, sequence analysis revealed a clear Shine-Dalgarno sequence but a lack of conserved overrepresented promoter motifs. These TSSs defined approximately 50 leaderless transcripts and an abundance of mRNAs with long leader regions of which 18 contain RNA regulatory elements from the Rfam database. The thiamine pyrophosphate riboswitch upstream of the thiC gene was examined using an in vivo assay with GFP-fusion vectors and shown to function via a translational repression mechanism. Furthermore, 56 novel intergenic small RNAs and 8 putative actuaton transcripts were detected, as well as 8 novel open reading frames (ORFs). This study illustrates how global mapping of TSSs can yield novel insights into the transcriptional features and RNA output of bacterial genomes.

[Germline mutations of TP53 gene among Chinese families with high risk for breast cancer].

OBJECTIVE: To evaluate the role of germline mutations of TP53 gene among a Chinese population with high risk for breast cancer. METHODS: A total of 81 BRCA-negative breast cancer probands from cancer families were analyzed using targeted capture and next-generation sequencing. Candidate mutations were verified with Sanger sequencing. Co-segregation analyses were carried out to explore the likely pathogenicity of the mutation. RESULTS: Of the 81 BRCA-negative patients, 3 exonic mutations in the TP53 gene were identified in 3 breast cancer patients. Of these, 2 mutations were previously reported and 1 was novel. One family with TP53 mutation has met the criteria for Li-Fraumeni syndrome (LFS) and accounted for 9.1% of all families who fulfilled the diagnostic criteria for LFS. Two of the carriers were diagnosed with breast cancer under the age of 30, and have accounted for 11.8% (2/17) of all very young (≤30 years) breast cancer patients in our study. CONCLUSION: The TP53 germline mutation is more common in Chinese population with a high risk for breast cancer than previously thought. TP53 gene mutation screening should be considered particularly for patients with a family history of LFS and very young age of onset.

[Overview and prospect of syndrome differentiation of hypertension in traditional Chinese medicine].

This article is to overview the literature of syndrome differentiation of traditional Chinese medicine on hypertension. According to the theory of disease in combination with syndrome, we concluded syndrome types of hypertension in four aspects, including national standards, industry standards, teaching standards and personal experience. Meanwhile, in order to provide new methods and approaches for normalized research, we integrated modern testing methods and statistical methods to analyze syndrome differentiation for the treatment of hypertension.

SLC35A2 expression drives breast cancer progression via ERK pathway activation.

Alterations in glycosylation are associated with breast tumor formation and progression. Nevertheless, the specific functions and mechanisms of the human major UDP-galactose transporter-encoding gene solute carrier family 35 member A2 (SLC35A2) in breast invasive carcinoma (BRCA) have not been fully determined. Here, we report that SLC35A2 promotes BRCA progression by activating extracellular signal regulated kinase (ERK). SLC35A2 expression and prognosis-predictive significance in pan-cancer were evaluated using public databases. The upstream non-coding RNAs (ncRNAs) of SLC35A2 were analyzed, and their expression and regulations were validated in breast tissues and cell lines by a quantitative PCR and dual-luciferase assays. We used bioinformatic tools to assess the link between SLC35A2 expression and immune infiltration and performed immunohistochemistry for validation. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, transwell, flow cytometer and western blotting were used to assess the proliferation, motility, cell cycle and apoptosis of BRCA cells in vitro. The xenograft models were constructed to assess the effect of SLC35A2 on BRCA tumor growth in vivo. The results indicated that SLC35A2 expression was upregulated and linked to an unfavorable prognosis in BRCA. The most likely upstream ncRNA-associated pathway of SLC35A2 in BRCA was the AC074117.1/hsa-let-7b-5p axis. SLC35A2 expression had positive correlations with the presence of Th2 cells, regulatory T cells and immune checkpoints. Knockdown of SLC35A2 could reduce BRCA cell proliferation, motility, and cause G2/M arrest and cell apoptosis via ERK signaling. Moreover, ERK activation can rescue the inhibitory effects of knockdown SLC35A2 in BRCA. In conclusion, AC074117.1/hsa-let-7b-5p axis-mediated high expression of SLC35A2 acts as a tumor promoter in BRCA via ERK signaling, which provides a potential target for BRCA treatment.

Poor condyle position after mandibular reconstruction and a classification system for patients with "VSCU" based on computed tomography: a cross-sectional study with retrospective data collection.

Background: Although the application of vascularized free bone muscle flap to reconstruct the mandible has become a standardized approach for mandible reconstruction, the results of its reconstruction are not always satisfactory. The purpose of this study was to identify the types of mandibular and condylar defects by analyzing the unsatisfactory cases of mandibular reconstruction in clinical practice, and to provide some clinical experience of reconstruction. Methods: Our study retrospectively analyzed 364 patients who underwent mandibular resection and vascularized free bone flap reconstruction of the mandible and temporomandibular joint (TMJ). We innovatively proposed a "VSCU" classification system (V: vertical position, S: sagittal position, C: coronal position, U: condylar resection is not required) by analyzing computed tomography (CT) scans of mandibular branches and TMJs. Results: In all, 221 cases of free iliac muscle flap and 143 cases of fibula muscle flap were included in this study, of which 23 cases had unsatisfactory results after TMJ reconstruction. We classified 23 patients with unsatisfactory mandibular reconstruction according to the "VSCU" classification system. The most common type was U + V + SfC (n=8), followed by V - SfC + U + (n=4), V - s + C + U + (n=3), V - sbcou - (n=3), V - SBC + U + (n=2), V - s + C + U - (n=1). The most common classification was insufficient mandibular rami length, followed by condylar sagittal anteriorization. There was no significant change in the position of condyle on the healthy side during mandibular reconstruction involving condyle. P1 on the affected side was 52.28±4.17 mm before operation and 58.94±5.65 mm after operation, P<0.01; P2 was 12.83±3.49 mm before operation and 24.90±7.15 mm after operation. S2 was 4.54±2.84 mm before operation and 19.10±8.54 mm after operation. A2 was 11.46±3.35 mm before operation and 24.15±8.29 mm after operation. The P values were all less than 0.01, and the differences were statistically significant. Conclusions: We propose to use the "VSCU" classification system for accurate 3-dimensional (3D) analysis and positioning, and then obtain accurate models through computer-aided design and manufacturing (CAD/CAM), which can reduce the occurrence of poor reconstruction effect and unreasonable joint position, and is worthy of clinical promotion.

Financial incentive interventions for smoking cessation among Chinese smokers: study protocol for a cluster randomised controlled trial.

INTRODUCTION: There is an urgent issue to relieve the burdens caused by tobacco use through feasible and effective smoking cessation interventions, particularly in a middle-income country with less accessible smoking cessation services and high demand for quitting smoking. Financial incentives have shown effective in changing health behaviours, thus needing to test its portability to a wider implementation and effectiveness of increasing smoking cessation rates. METHODS AND ANALYSIS: This is a three-arm cluster randomised controlled trial. 462 eligible participants will be assigned to 2 financial incentive groups-rewards or deposits, or the control group. All participants including those in the control group will receive text messages to help quitting smoking developed by the US National Cancer Institute over a 3-month intervention period. In addition to text messages, reward group participants will be rewarded with CNY200 and CNY400 (CNY100 approximately US$15) for sustained smoking abstinence at 1 month and 3 months follow-up assessments; participants in the deposit group will accumulate CNY200 and CNY600 in the deposit accounts after verified smoking abstinence at 1 month and 3 months follow-up assessments, and all the deposits will be given at once right after the 3-month follow-up visit. The primary outcome is biochemically verified smoking abstinence rate sustained for 6 months after enrolment. ETHICS AND DISSEMINATION: This trial protocol has been approved by the Ethics Committee of Peking University Health Science Centre (date: 23 February 2023; ethical approval number: IRB00001052-22172). Results and findings of this trial will be disseminated in peer-reviewed journals and professional conferences. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-2300069631.