Image-Guided Photothermal and Immune Therapy of Tumors via Melanin-Producing Genetically Engineered Bacteria.

Photothermal therapy (PTT) is a new treatment modality for tumors. However, the efficient delivery of photothermal agents into tumors remains difficult, especially in hypoxic tumor regions. In this study, an approach to deliver melanin, a natural photothermal agent, into tumors using genetically engineered bacteria for image-guided photothermal and immune therapy is developed. An Escherichia coli MG1655 is transformed with a recombinant plasmid harboring a tyrosinase gene to produce melanin nanoparticles. Melanin-producing genetically engineered bacteria (MG1655-M) are systemically administered to 4T1 tumor-bearing mice. The tumor-targeting properties of MG1655-M in the hypoxic environment integrate the properties of hypoxia targeting, photoacoustic imaging, and photothermal therapeutic agents in an "all-in-one" manner. This eliminates the need for post-modification to achieve image-guided hypoxia-targeted cancer photothermal therapy. Tumor growth is significantly suppressed by irradiating the tumor with an 808 nm laser. Furthermore, strong antitumor immunity is triggered by PTT, thereby producing long-term immune memory effects that effectively inhibit tumor metastasis and recurrence. This work proposes a new photothermal and immune therapy guided by an "all-in-one" melanin-producing genetically engineered bacteria, which can offer broad potential applications in cancer treatment.

Prevention of the Lachnum polysaccharide and its selenium derivatives on cisplatin-induced acute kidney injury in mice.

To investigate the renal protective effects of the polysaccharide LEP-1a and derivatives of selenium (SeLEP-1a) from Lachnum YM38, cisplatin (CP) was used to establish an acute kidney model. LEP-1a and SeLEP-1a could effectively reverse the decrease in renal index and improved renal oxidative stress. LEP-1a and SeLEP-1a significantly reduced the contents of the inflammatory cytokines. They could inhibit the release of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). At the same time, the PCR results indicated that SeLEP-1a could significantly inhibit the mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor-kB (NF-κB) p65 and inhibitor of kappa B-alpha (IκBα). Western blot analysis showed that LEP-1a and SeLEP-1a significantly downregulated the expression levels of Bcl-2-associated X protein (Bax) and cleaved caspase-3 and upregulated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl-2) protein expression levels in the kidney. LEP-1a and SeLEP-1a could improve CP-induced acute kidney injury by regulating the oxidative stress response, NF-κB-mediated inflammation and the PI3K/Akt-mediated apoptosis signalling pathway.

Copper Atom Pairs Stabilize *OCCO Dipole Toward Highly Selective CO2 Electroreduction to C2H4.

Deeply electrolytic reduction of carbon dioxide (CO2) to high-value ethylene (C2H4) is very attractive. However, the sluggish kinetics of C-C coupling seriously results in the low selectivity of CO2 electroreduction to C2H4. Herein, we report a copper-based polyhedron (Cu2) that features uniformly distributed and atomically precise bi-Cu units, which can stabilize *OCCO dipole to facilitate the C-C coupling for high selective C2H4 production. The C2H4 faradaic efficiency (FE) reaches 51 % with a current density of 469.4 mA cm-2, much superior to the Cu single site catalyst (Cu SAC) (~0 %). Moreover, the Cu2 catalyst has a higher turnover frequency (TOF, ~520 h-1) compared to Cu nanoparticles (~9.42 h-1) and Cu SAC (~0.87 h-1). In situ characterizations and theoretical calculations revealed that the unique Cu2 structural configuration could optimize the dipole moments and stabilize the *OCCO adsorbate to promote the generation of C2H4.

Commercializable Naphthalene Diimide Anolytes for Neutral Aqueous Organic Redox Flow Batteries.

Neutral aqueous organic redox flow batteries (AORFBs) hold the potential to facilitate the transition of renewable energy sources from auxiliary to primary energy, the commercial production of anolyte materials still suffers from insufficient performance of high-concentration and the high cost of the preparation problem. To overcome these challenges, this study provides a hydrothermal synthesis methodology and introduces the charged functional groups into hydrophobic naphthalene diimide cores, and prepares a series of high-performance naphthalene diimide anolytes. Under the synergistic effect of π-π stacking and H-bonding networks, the naphthalene diimide exhibits excellent structural stability and the highest water solubility (1.85 M for dex-NDI) reported to date. By employing the hydrothermal method, low-cost naphthalene diimides are successfully synthesized on a hundred-gram scale of $0.16 g-1 ($2.43 Ah-1), which is also the lowest price reported to date. The constructed full battery achieves a high electron concentration of 2.4 M, a high capacity of 54.4 Ah L-1, and a power density of 318 mW cm-2 with no significant capacity decay observed during long-duration cycling. These findings provide crucial support for the commercialization of AORFBs and pave the way for revolutionary developments in neutral AORFBs.

Biosynthesis of Melanin Nanoparticles for Photoacoustic Imaging Guided Photothermal Therapy.

Photothermal therapy (PTT) has attracted considerable attention in recent years due to their unique advantages in minimal invasiveness and spatiotemporal selectivity. However, the fabrication procedures of PTT agents frequently require complex chemical and/or physical methods that involves harsh and environmentally hazardous conditions. Here, a genetically engineered bacterium is developed to synthesize melanin nanoparticles under mild and environmentally friendly conditions. The biosynthetic melanin nanoparticles exhibit excellent biocompatibility, good stability, and negligible toxicity. In addition, the biosynthetic melanin nanoparticles have strong absorption at near-infrared (NIR) region and higher photothermal conversion efficiency (48.9%) than chemically synthesized melanin-like polydopamine nanoparticles under an 808 nm laser irradiation. Moreover, the results show that the biosynthetic melanin nanoparticles have excellent photoacoustic imaging (PAI) performance and can be used for PAI guided PTT in vivo. In conclusion, the study provides an alternative approach to synthesize PTT agents with broad application potential in the diagnosis and treatment of cancer.

Association between snoring, daytime sleepiness and cardiovascular disease in Chinese rural adults.

BACKGROUNDS AND AIMS: Evidence on the association between habitual snoring, excessive daytime sleepiness (EDS), and cardiovascular diseases (CVDs) remains uncertain and limited. The study aimed to explore the independent and joint association between habitual snoring, EDS, and CVDs in rural Chinese adults. METHODS AND RESULTS: A total of 28,140 participants from the Henan rural cohort study were included. Sleep status information was obtained by self-reported. Based on their sleep status, the participants were classified into four groups: "no snoring and no EDS (NSNS) (reference group)", "snoring and no EDS (SNS)", "no snoring and EDS (NSS)", "snoring and EDS (SS)." The logistic regression models were used to calculate independent and joint odds ratios (OR) and 95% confidence intervals (CI) between the snoring, EDS status and stroke, CHD, and CVD. Of the 28,140 participants, 740 subjects reported snoring and sleepiness. The ORs and (95% CIs) for CVDs in the adjusted model were 1.31 (1.20-1.43) for participants who snored frequently and 2.44 (1.76-3.39) for frequent sleepiness compared with no snoring and no sleepiness. Individuals with both snoring and sleepiness had higher odds of CVDs compared with no snoring and no sleepiness (OR: 2.18, 95%CI: 1.80-2.62). CONCLUSION: Habitual snoring and excessive daytime sleepiness were independently and jointly associated with CVDs in the Chinese rural population. More studies are needed to explore the mechanisms of the relationship. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-52 07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375.

Prevalence and morphological subtype distributions of anaemia in a Chinese rural population: the Henan Rural Cohort study.

OBJECTIVE: This study aimed to evaluate the recent prevalence and the distributions of morphological subtypes of anaemia in the rural population. DESIGN: Anaemia was defined according to the WHO and the Chinese criteria, and the morphological subtypes of anaemia were classified based on the erythrocyte parameters. The age-standardised prevalence was calculated according to the data of the Population Census 2010 in China. SETTING: A cross-sectional study in Henan Province. PARTICIPANTS: 33 585 subjects aged 18-79 years old. RESULTS: The standardised prevalence of anaemia across the WHO and the Chinese definitions was 13·63 % and 5·45 %, respectively. Regardless of which criteria was used, the standardised prevalence of anaemia was higher among women than among men and that increased with age in men, while markedly decreased after menopause in women. There were shifts in morphological patterns of anaemia using the WHO and the Chinese criteria that the standardised prevalence of microcytic anaemia was 3·74 % and 2·97 %, normocytic anaemia was 9·20 % and 2·34 %, and macrocytic anaemia was 0·75 % and 0·14 %, respectively. Besides, there were differences in the influencing factors of anaemia according to different criteria or gender. However, age, education level and renal damage were consistently significantly associated with anaemia in all participants. CONCLUSIONS: Anaemia may still be a serious health problem in rural China. It is necessary to reformulate prevention and management strategies to reduce the disease burden of anaemia.

The independent and combined association of napping and night sleep duration with stroke in Chinese rural adults.

BACKGROUND: Inappropriate sleep duration is a potential cause of stroke. But the effect of napping on stroke risk remains controversial and the interaction between night sleep and napping duration remains unclear. The objective of this study was to examine the independent and combined effects of napping and nocturnal sleep duration on stroke. METHODS: Subjects were derived from a rural cohort study in Henan. The Pittsburgh Sleep Quality Index (PSQI) was applied to identify nap duration and nocturnal sleep duration. Binary logistic regression was employed to indicate the dose-response relationships between naps, nocturnal sleep, total 24-h sleep duration, and stroke. RESULTS: Among the 37,341 participants (14,485 men), 2600 suffered from a stroke. The odds ratios (ORs) and 95% confidence level (CI) for stroke in the fully adjusted model were 1.37 (1.13-1.65) for men nappers compared to non-nappers. Compared to 7-8 h of sleep per day, night sleep durations < 6 h and ≥ 9 h and 24-h sleep duration ≥ 10 h were linked to increased odds of stroke in men. The ORs (95%CI) were 1.34 (1.06-1.69) in nocturnal sleep duration < 6 h, 1.30 (1.06-1.59) in nocturnal sleep duration ≥ 9 h, and 1.40 (1.15-1.71) in 24-h sleep duration ≥ 10 h in men. In addition, long naps and prolonged nocturnal sleep duration have a joint effect on stroke in the fully adjusted model. CONCLUSION: The napping duration and nocturnal sleep duration have independently and jointly effects on stroke in rural populations. More research is required to explore the underlying mechanisms for this relationship. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered on the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) ( http://www.chictr.org.cn/showproj.aspx?proj=11375 ).

Role of circRNA in pathogenesis of Alzheimer's disease. / 环状RNAåœ¨é˜¿å°”èŒ¨æµ·é»˜ç— å‘ç— æœºåˆ¶ä¸­çš„ä½œç”¨.

Circular RNA (circRNA) is a covalently closed-loop non-coding RNA that exists widely in the transcriptome of eukaryotic cells. It participates in a variety of pathophysiological processes by acting as a microRNA sponge, regulating the level of protein transcription, and interacting with RNA binding proteins. CircRNA is enriched in the cortex, hippocampus, brain white matter, and photoreceptor neurons of aging bodies, and they can be used as a biomarker for neural senescence. The expression levels of circRNA in peripheral blood and synapses in Alzheimer's disease (AD) patients are increased, which are involved in the occurrence and prognosis of AD. Different circRNAs such as HDAC9, Homer1, Cwc27, Tulp4, and PTK2 can lead to AD pathological changes via increasing amyloid-ß deposition, promoting tau protein hyperphosphorylation, aggravating neuroinflammation and mitochondrial dysfunction, which result in the cognitive decline.

Bacteria-Triggered Solar Hydrogen Production via Platinum(II)-Tethered Chalcogenoviologens.

Multifunctional solar energy conversion offers a feasible strategy to solve energy, environmental and water crises. Herein, a series of platinum(II)-tethered chalcogenoviologens (PtL+ -EV2+ , E=S, Se, Te) is reported, which integrate the functions of photosensitizer, electron mediator and catalyst. PtL+ -EV2+ (particularly for PtL+ -SeV2+ )-based one-component solar H2 production could be triggered not only by EDTA, but also by facultative anaerobic and aerobic bacteria relying on a simplified mechanism, along with efficient antibacterial activities. In addition, by using real pool water, PtL+ -SeV2+ achieved multiple functions, including H2 production, antibacterial action and acid removal, which supplied a new strategy to solve various problems in real life via a single system.

A "Self-Checking" pH/Viscosity-Activatable NIR-II Molecule for Real-Time Evaluation of Photothermal Therapy Efficacy.

We present a second near-infrared (NIR-II) self-checking molecule, LET-1052, for acidic tumor microenvironment (TME) turn-on photothermal therapy (PTT), followed by viscosity based therapeutic efficacy evaluation by itself in two independent channels, denoted as "self-checking" strategy. In acidic TME, LET-1052 was protonated and turned on NIR-II absorption for PTT under 1064 nm laser irradiation. Subsequently, PTT-induced cellular death increases intracellular viscosity, which inhibited the intramolecular rotation of LET-1052, resulting in the enhancement of NIR-I fluorescence for real-time evaluation of PTT efficacy. After PTT of tumor-bearing mice for different periods of NIR-II laser irradiation, NIR-I fluorescence in the tumor region showed positive correlation with tumor growth inhibition rate, demonstrating reliable and prompt prediction of PTT efficacy. The strategy may be expanded for instant evaluation of other therapeutic modalities for personalized medicine.

Associations of midpoint of sleep and night sleep duration with type 2 diabetes mellitus in Chinese rural population: the Henan rural cohort study.

BACKGROUND: The study aimed to investigate the independent and combined effects of midpoint of sleep and night sleep duration on type 2 diabetes mellitus (T2DM) in areas with limited resources. METHODS: A total of 37,276 participants (14,456 men and 22,820 women) were derived from the Henan Rural Cohort Study. Sleep information was assessed based on the Pittsburgh Sleep Quality Index. Logistic regression models and restricted cubic splines were used to estimate the relationship of the midpoint of sleep and night sleep duration with T2DM. RESULTS: Of the 37,276 included participants, 3580 subjects suffered from T2DM. The mean midpoint of sleep among the Early, Intermediate and Late groups were 1:05 AM ±23 min, 1:56 AM ±14 min, and 2:57 AM ±34 min, respectively. Compared to the Intermediate group, adjusted odds ratios (ORs) and 95% confidence interval (CI) of T2DM were 1.13 (1.04-1.22) and 1.14 (1.03-1.26) in the Early group and the Late group. Adjusted OR (95% CI) for T2DM compared with the reference (7- h) was 1.28 (1.08-1.51) for longer (≥ 10 h) night sleep duration. The combination of late midpoint of sleep and night sleep duration (≥ 9 h) increased 38% (95% CI 10-74%) prevalence of T2DM. These associations were more obvious in women than men. CONCLUSIONS: Late and early midpoint of sleep and long night sleep duration were all associated with higher prevalence of T2DM. Meanwhile, midpoint of sleep and night sleep duration might have combined effects on the prevalence of T2DM, which provided potential health implications for T2DM prevention, especially in rural women. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699 ). Date of registration: 2015-07-06.

Long-term exposure to ambient PM1 strengthened the association of depression/anxiety symptoms with poor sleep quality: The Henan Rural Cohort study.

Evidence from numerous epidemiological studies for the relationship between mental disorder and sleep quality was inconclusive and few studies assessed the modification effect of exposure to ambient air PM1 (particulate matter with an aerodynamic diameter ≤ 1.0 µm) on this association. In this study, 27,572 participants aged 18-79 years from The Henan Rural Cohort study were included in the final analyses. The Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) scales were used to estimate the frequency of depression and anxiety symptoms of all participants, respectively. The Pittsburgh Sleep Quality Index (PSQI) scale was used to assess night sleep quality and PSQI global score (GSC) ≥ 6 was classified as poor sleep quality. The three-year average exposure concentration of PM1 before the baseline survey was determined as long-term exposure concentration of ambient PM1. Logistic regression model was conducted to estimate the independent or joint effect of depression/anxiety symptoms and ambient PM1 exposure on poor sleep quality. In the adjusted models, the odds ratios (ORs) and 95% confidence intervals (95% CIs) of poor sleep quality associated with depression and anxiety symptoms were 3.75 (3.37, 4.17) and 3.42 (3.06, 3.81), respectively, and that associated with long-term exposure to PM1 was 1.06 (1.03, 1.09). An interaction effect was observed between anxiety symptoms score and PM1 concentration on poor sleep quality. With the increment of PM1 concentration, the association was strengthened between depression/anxiety symptoms and poor sleep quality. Besides, compared with the reference group, the ORs (95% CIs) of poor sleep quality in those with comorbidity of depression and anxiety symptoms were 4.98 (3.95, 6.29), 5.23 (3.98, 6.87), 5.76 (4.42, 7.49), and 5.58 (3.83, 8.14), respectively, from the first to the fourth quartile level of the PM1 concentration. These findings suggested that long-term exposure to PM1 strengthened the association of depression/anxiety symptoms with poor sleep quality in rural China.

High-throughput sequencing analysis of the rhizosphere arbuscular mycorrhizal fungi (AMF) community composition associated with Ferula sinkiangensis.

BACKGROUND: Ferula sinkiangensis is an increasingly endangered medicinal plant. Arbuscular mycorrhiza fungi (AMF) are symbiotic microorganisms that live in the soil wherein they enhance nutrient uptake, stress resistance, and pathogen defense in host plants. While such AMF have the potential to contribute to the cultivation of Ferula sinkiangensis, the composition of AMF communities associated with Ferula sinkiangensis and the relationship between these fungi and other pertinent abiotic factors still remains to be clarified. RESULTS: Herein, we collected rhizosphere and surrounding soil samples at a range of depths (0-20, 20-40, and 40-60 cm) and a range of slope positions (bottom, middle, top). These samples were then subjected to analyses of soil physicochemical properties and high-throughput sequencing (Illumina MiSeq). We determined that Glomus and Diversispora species were highly enriched in all samples. We further found that AMF diversity and richness varied significantly as a function of slope position, with this variation primarily being tied to differences in relative Glomus and Diversispora abundance. In contrast, no significant relationship was observed between soil depth and overall AMF composition, although some AMF species were found to be sensitive to soil depth. Many factors significantly affected AMF community composition, including organic matter content, total nitrogen, total potassium, ammonium nitrogen, nitrate nitrogen, available potassium, total dissolvable salt levels, pH, soil water content, and slope position. We further determined that Shannon diversity index values in these communities were positively correlated with total phosphorus, nitrate-nitrogen levels, and pH values (P < 0.05), whereas total phosphorus, total dissolvable salt levels, and pH were positively correlated with Chao1 values (P < 0.05). CONCLUSION: In summary, our data revealed that Glomus and Diversispora are key AMF genera found within Ferula sinkiangensis rhizosphere soil. These fungi are closely associated with specific environmental and soil physicochemical properties, and these soil sample properties also differed significantly as a function of slope position (P < 0.05). Together, our results provide new insights regarding the relationship between AMF species and Ferula sinkiangensis, offering a theoretical basis for further studies of their development.

Rapid detection of Bombyx mori bidensovirus by loop-mediated isothermal amplification based lateral flow dipstick assay for field applications.

Bombyx mori bidensovirus (BmBDV), is the only bipartite single-stranded DNA (ssDNA) insect virus reported to date. BmBDV causes fatal flacherie disease in silkworm, resulting in large economic losses to sericulture. We developed a loop-mediated isothermal amplification with lateral flow dipstick (LAMP-LFD) method that can successfully and rapidly detect BmBDV DNA with a low limit of detection (5 fg, 400 copies of the BmBDV genome). The method was evaluated and improved for direct field diagnosis using silkworm faeces. In the field, the actual limit of detection was ∼50 fg (4000 copies of the BmBDV genome). The results demonstrated that, compared with traditional methods for BmBDV detection, our new LAMP-LFD method was much more rapid, sensitive and cost-effective, with less dependence on equipment, making it easier to use. The method has potential to be translated into a new diagnostic product for field applications in the sericulture industry.

A Sodium-Ion-Conducting Direct Formate Fuel Cell: Generating Electricity and Producing Base.

A barrier that limits the development of the conventional cation-exchange membrane direct liquid fuel cells (CEM-DLFCs) is that the CEM-DLFCs need additional base to offer both alkaline environment and charge carriers. Herein, we propose a Na+ -conducting direct formate fuel cell (Na-DFFC) that is operated in the absence of added base. A proof-of-concept Na-DFFC yields a peak power density of 33 mW cm-2 at 60 °C, mainly because the hydrolysis of sodium formate provides enough OH- and Na+ ions, proving the conceptual feasibility. Moreover, contrary to the conventional chlor-alkali process, this Na-DFFC enables to generate electricity and produce NaOH simultaneously without polluting the environment. The Na-DFFC runs stably during 13 hours of continuous operation at a constant current of 10 mA, along with a theoretical production of 195 mg NaOH. This work presents a new type of electrochemical conversion device that possesses a wide range of potential applications.

Crystal structures of enterovirus 71 (EV71) recombinant virus particles provide insights into vaccine design.

Hand-foot-and-mouth disease (HFMD) remains a major health concern in the Asia-Pacific regions, and its major causative agents include human enterovirus 71 (EV71) and coxsackievirus A16. A desirable vaccine against HFMD would be multivalent and able to elicit protective responses against multiple HFMD causative agents. Previously, we have demonstrated that a thermostable recombinant EV71 vaccine candidate can be produced by the insertion of a foreign peptide into the BC loop of VP1 without affecting viral replication. Here we present crystal structures of two different naturally occurring empty particles, one from a clinical C4 strain EV71 and the other from its recombinant virus containing an insertion in the VP1 BC loop. Crystal structure analysis demonstrated that the inserted foreign peptide is well exposed on the particle surface without significant structural changes in the capsid. Importantly, such insertions do not seem to affect the virus uncoating process as illustrated by the conformational similarity between an uncoating intermediate of another recombinant virus and that of EV71. Especially, at least 18 residues from the N terminus of VP1 are transiently externalized. Altogether, our study provides insights into vaccine development against HFMD.

Crystal Structures of Yeast-Produced Enterovirus 71 and Enterovirus 71/Coxsackievirus A16 Chimeric Virus-Like Particles Provide the Structural Basis for Novel Vaccine Design against Hand-Foot-and-Mouth Disease.

UNLABELLED: Human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents for hand-foot-and-mouth disease (HFMD). Previously, we demonstrated that a virus-like particle (VLP) for EV71 produced from Saccharomyces cerevisiae is a potential vaccine candidate against EV71 infection, and an EV71/CVA16 chimeric VLP can elicit protective immune responses against both virus infections. Here, we presented the crystal structures of both VLPs, showing that both the linear and conformational neutralization epitopes identified in EV71 are mostly preserved on both VLPs. The replacement of only 4 residues in the VP1 GH loop converted strongly negatively charged surface patches formed by portions of the SP70 epitope in EV71 VLP into a relatively neutral surface in the chimeric VLP, which likely accounted for the additional neutralization capability of the chimeric VLP against CVA16 infection. Such local variations in the amino acid sequences and the surface charge potential are also present in different types of polioviruses. In comparison to EV71 VLP, the chimeric VLP exhibits structural changes at the local site of amino acid replacement and the surface loops of all capsid proteins. This is consistent with the observation that the VP1 GH loop located near the pseudo-3-fold junction is involved in extensive interactions with other capsid regions. Furthermore, portions of VP0 and VP1 in EV71 VLP are at least transiently exposed, revealing the structural flexibility of the VLP. Together, our structural analysis provided insights into the structural basis of enterovirus neutralization and novel vaccine design against HFMD and other enterovirus-associated diseases. IMPORTANCE: Our previous studies demonstrated that the enterovirus 71 (EV71) virus-like particle (VLP) produced from yeast is a vaccine candidate against EV71 infection and that a chimeric EV71/coxsackievirus A16 (CVA16) VLP with the replacement of 4 amino acids in the VP1 GH loop can confer protection against both EV71 and CVA16 infections. This study reported the crystal structures of both the EV71 VLP and the chimeric EV71/CVA16 VLP and revealed that the major neutralization epitopes of EV71 are mostly preserved in both VLPs. In addition, the mutated VP1 GH loop in the chimeric VLP is well exposed on the particle surface and exhibits a surface charge potential different from that contributed by the original VP1 GH loop in EV71 VLP. Together, this study provided insights into the structural basis of enterovirus neutralization and evidence that the yeast-produced VLPs can be developed into novel vaccines against hand-foot-and-mouth disease (HFMD) and other enterovirus-associated diseases.

Human enterovirus 71 uncoating captured at atomic resolution.

UNLABELLED: Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children, and structural characterization of EV71 during its life cycle can aid in the development of therapeutics against HFMD. Here, we present the atomic structures of the full virion and an uncoating intermediate of a clinical EV71 C4 strain to illustrate the structural changes in the full virion that lead to the formation of the uncoating intermediate prepared for RNA release. Although the VP1 N-terminal regions observed to penetrate through the junction channel at the quasi-3-fold axis in the uncoating intermediate of coxsackievirus A16 were not observed in the EV71 uncoating intermediate, drastic conformational changes occur in this region, as has been observed in all capsid proteins. Additionally, the RNA genome interacts with the N-terminal extensions of VP1 and residues 32 to 36 of VP3, both of which are situated at the bottom of the junction. These observations highlight the importance of the junction for genome release. Furthermore, EV71 uncoating is associated with apparent rearrangements and expansion around the 2- and 5-fold axes without obvious changes around the 3-fold axes. Therefore, these structures enabled the identification of hot spots for capsid rearrangements, which led to the hypothesis that the protomer interface near the junction and the 2-fold axis permits the opening of large channels for the exit of polypeptides and viral RNA, which is an uncoating mechanism that is likely conserved in enteroviruses. IMPORTANCE: Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children. EV71 contains an RNA genome protected by an icosahedral capsid shell. Uncoating is essential in EV71 life cycle, which is characterized by conformational changes in the capsid to facilitate RNA release into host cell. Here we present the atomic structures of the full virion and an uncoating intermediate of a clinical C4 strain of EV71. Structural analysis revealed drastic conformational changes associated with uncoating in all the capsid proteins near the junction at the quasi-3-fold axis and protein-RNA interactions at the bottom of the junction in the uncoating intermediate. Significant capsid rearrangements also occur at the icosahedral 2- and 5-fold axes but not at the 3-fold axis. Taking the results together, we hypothesize that the junction and nearby areas are hot spots for capsid breaches for the exit of polypeptides and viral RNA during uncoating.

Diversity of Arbuscular Mycorrhizal Fungi of the Rhizosphere of Lycium barbarum L. from Four Main Producing Areas in Northwest China and Their Effect on Plant Growth.

Arbuscular mycorrhizal fungi (AMF) can help plants absorb more mineral nutrients after they colonize plant roots, and the mycelia harmonize the soil structure and physical and chemical properties by secreting compounds. AMF species co-evolve with their habitat's geographic conditions and hosts; this gradually causes differences in the AMF species. By using Melzer's reagent to analyze the morphology and using Illumina Miseq sequencing technology to perform the molecular identification of AMF communities among the four typical L. barbarum planting areas (Zhongning, Guyuan, Jinghe, and Dulan) investigated, the variety of L. barbarum roots and rhizosphere AMF communities was greater in the Zhongning area, and every region additionally had endemic species. The successfully amplified AMF was re-applied to the L. barbarum seedlings. We found that the total dry weight and accumulation of potassium increased significantly (p < 0.05), and the root volume and number of root branches were significantly higher in the plants that were inoculated with Paraglomus VTX00375 in the pot experiment, indicating that AMF improves root development and promotes plant growth. We have investigated AMF germplasm species in four regions, and we are committed to the development of native AMF resources. The multiplication and application of AMF will be conducive to realizing the potential role of biology in the maintenance of agroecology.