Molecular Mechanism of Adenovirus Late Protein L4-100K Chaperones the Trimerization of Hexon.

Assembly of the adenovirus capsid protein hexon depends on the assistance of the molecular chaperone L4-100K. However, the chaperone mechanisms remain unclear. In this study, we found that L4-100K was involved in the hexon translation process and could prevent hexon degradation by the proteasome in cotransfected human cells. Two nonadjacent domains, 84-133 and 656-697, at the N-terminal and C-terminal regions of human adenovirus type 5 L4-100K, respectively, were found to be crucial and cooperatively responsible for hexon trimer expression and assembly. These two chaperone-related domains were conserved in the sequence of L4-100K and in the function of hexon assembly across different adenovirus serotypes. Different degrees of cross-activity of hexon trimerization with different serotypes were detected in subgroups B, C, and D, which were proven to be controlled by the interaction between the C-terminal chaperone-related domain of L4-100K and hypervariable regions (HVR) of hexon. Additionally, HVR-chimeric hexon mutants were successfully assembled with the assistance of the 1-697 mutant. Structural analysis of 656-697 by nuclear magnetic resonance and structural prediction of L4-100K using Robetta showed that the two conserved domains are mainly composed of α-helices and are located on the surface of the highly folded core region. Our research provides a more complete understanding of hexon assembly and guidance for the development of hexon-chimeric adenovirus vectors that will be safer, smarter, and more efficient. IMPORTANCE Adenovirus vectors have been widely used in clinical trials of vaccines and gene therapy, although some deficiencies remain. Chimeric modification of the hexon was expected to improve the potency of preexisting immune evasion and targeting, but in many cases, viral packaging is prevented by the inability of the chimeric hexon to assemble correctly. So far, few studies have examined the mechanisms of hexon trimer assembly. Here, we show how the chaperone protein L4-100K contributes to the assembly of the adenovirus capsid protein hexon, and these data will provide a guide for novel adenovirus vector design and development, as we desired.

Self-amplified activatable nanoprodrugs for enhanced chemodynamic/chemo combination therapy.

Chemodynamic therapy (CDT) has gained increasing attention by virtue of its high tumor specificity and low side effect. However, the low concentration of hydrogen peroxide (H2O2) in the tumor site suppresses the therapeutic efficacy of CDT. To improve the efficacy, introducing other kind of therapeutic modality is a feasible choice. Herein, we develop a self-amplified activatable nanomedicine (PCPTH NP) for chemodynamic/chemo combination therapy. PCPTH NP is composed of a H2O2-activatable amphiphilic prodrug PEG-PCPT and hemin. Upon addition of H2O2, the oxalate linkers within PCPTH NP are cleaved, which makes the simultaneous release of CPT and hemin. The released CPT can not only kill cancer cells but also upregulate the intracellular reactive oxygen species (ROS) level. The elevated ROS level may accelerate the release of drugs and enhance the CDT efficacy. PCPTH NP shows a H2O2concentration dependent release profile, and can effectively catalyze H2O2into hydroxyl radical (·OH) under acidic condition. Compared with PCPT NP without hemin, PCPTH NP has better anticancer efficacy bothin vitroandin vivowith high biosafety. Thus, our study provides an effective approach to improve the CDT efficacy with high tumor specificity.

Mechanical stretch facilitates tenomodulin expression to induce tenocyte migration via MAPK signaling pathway.

Tenomodulin (Tnmd) is a type II transmembrane glycoprotein that regulates tendon development and maturation. Our previous study indicated that mechanical stretch could induce Tnmd expression to promote tenocyte migration, associated with reinforcement of fibrous actin (F-actin) stress fibers and chromatin decondensation. However, the detailed molecular mechanisms of this processes are far from clear. Activation of mitogen-activated protein kinase (MAPK) signaling occurs in response to various extracellular stimuli and controls a large number of fundamental cellular processes. The present study we investigated the influence of MAPK signaling on mechanical stretch-induced Tnmd expression and its action way. Expression and activities of extracellular signal-related kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38 MAPK (p38) were determined by Western blot. Cell migration was detected by Transwell assay. Immunofluorescence staining was used to detect F-actin stress fibers. Nuclear chromatin decondensation was detected by in situ DNaseI sensitivity assay. It was found that mechanical stretch promoted Tnmd expression by activating ERK1/2, JNK and p38 signaling. The inhibition of the ERK1/2, JNK or p38 repressed mechanical stretch-promoted tenocyte migration and mechanical stretch-induced reinforcement of F-actin stress fibers. However, only ERK1/2 and p38 inhibitor could repress mechanical stretch-induced chromatin decondensation, and the JNK inhibitor had no significant effect. Moreover, latrunculin (Lat A), the most widely used reagent to depolymerize actin filaments, could inhibit the stretch-induced chromatin decondensation. Taken together, our findings elucidated a molecular pathway by which a mechanical signal is transduced via activation of MAPK signaling to influence reinforcement of F-actin stress fibers and chromatin decondensation, which could further lead Tnmd expression to promote tenocyte migration.

Long-term poor sleep quality is associated with adverse donor reactions in college students in Central China: A population-based cross-sectional study.

BACKGROUND AND OBJECTIVES: Adverse donor reaction (ADR) could adversely impact the recruitment and retention of blood donors, but the evidence of effect of sleep quality on ADR is limited and controversial. The goal of this study was to explore the association between the sleep quality and ADR among college students in Wuhan. MATERIALS AND METHODS: The college student blood donors in Wuhan from March to May 2022 were recruited. Self-compiled general information questionnaire and Pittsburgh sleep quality index (PSQI) were investigated by convenience sampling. Univariable and multivariable logistic regression analyses were used to estimate the association. RESULTS: Among 1014 participants included in this study, 63 were in the ADR group and 951 were in the non-ADR group. Compared with the non-ADR group, the PSQI scores of ADR group were higher (3.44 ± 1.81 vs. 2.78 ± 1.82, p < 0.01). The results of multivariable logistic regression analysis showed that after adjusting gender, body mass index, blood donation history and other potential confounding factors, higher PSQI scores were related to the occurrence of ADRs (odds ratio = 1.231, 95% confidence interval 1.075-1.405), that is, the worse the sleep quality, the more likely the ADRs will occur. CONCLUSION: The long-term poor sleep quality of college students is a risk factor for the occurrence of ADRs. It should be identified early before blood donation to reduce the incidence of ADRs and improve the safety and satisfaction of donors.

Mechanical stretch promotes tenocyte migration via chromatin remodelling-mediated nuclear morphology changes.

Wound healing and function recovery of injured tendons are still a big challenge for orthopaedic surgery. Evidence in clinic shows that early controlled motion has significant favourable effects on tendon healing; however, the mechanisms involved in are not fully understood. In the present study, it was shown that an appropriate mechanical stretch (10% strain, 0.5 Hz for 1 h) evidently promotes rat tenocyte migration and nuclear morphology changes. The farther research discovered that mechanical stretch had no effect on Lamin A/C expression, but it could promote chromatin decondensation. Moreover, the histone modification plays an important role in mechanical stretch-mediated chromatin decondensation. Inhibition histone modification could inhibit mechanical stretch-promoted nuclear morphology changes and tenocyte migration. These results indicating that mechanical stretch may promote tenocyte migration via chromatin remodelling-mediated nuclear morphology changes, which contribute to a better understanding of the role of mechanical stretch on tenocyte migration and repair of injured tendon.

Correlation between mortality and blood transfusion in patients with major surgery initially admitted to intensive care unit: a retrospective analysis.

PURPOSE: Transfusing red blood cells promptly corrects anemia and improves tissue oxygenation in around 40% of patients hospitalized in the intensive care unit (ICU) after major surgical operations. This study's goal is to investigate how blood transfusions affect the mortality rates of patients after major surgery who are hospitalized in the ICU. METHODS: Retrospective research was done on recently hospitalized patients who had major procedures in the ICU between October 2020 and February 2022 at the Huanggang Central Hospital of Yangtze University, China. The patients' prognoses at three months were used to classify them as either survivors or deceased. Patient demographic information, laboratory results, and blood transfusion histories were acquired, and the outcomes of the two groups were compared based on the differences. Univariate and multivariate logistic regression analyses were used to examine the prognosis of surgical disease patients first admitted to the ICU. The receiver operating characteristic (ROC) curve was used to evaluate the predictive power of each risk factor. The relationship between transfusion frequency, transfusion modality, and patient outcome was examined using Spearman's correlation analysis. RESULTS: Data from 384 patients was included in the research; of them, 214 (or 55.7%) died within three months of their first stay in the ICU. The death group had higher scores on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) than the survival group did (all P < 0.05); the death group also had lower scores on the Glasgow Coma Scale, systolic blood pressure, hemoglobin, platelet distribution width, and blood transfusion ratio. Multivariate logistic regression analysis revealed an odds ratio (OR) of 1.654 (1.281-1.989), a 95% confidence interval (CI) of 1.440 (1.207-1.701), and a P value of 0.05 for death in patients undergoing major surgery who were hospitalized to the intensive care unit (ICU). Areas under the ROC curve (AUC) of 0.836, 0.799, and 0.871, respectively, and 95% CIs of 0.796-0.875, 0.755-0.842, and 0.837-0.904, respectively, all P0.05, had significant predictive value for patients initially admitted to the ICU and for APACHE II score > = 12 points, SOFA score > = 6, and blood transfusion. When all three indicators were used jointly to predict a patient's prognosis after major surgery, the accuracy increased to 86.4% (sensitivity) and 100% (specificity). There was a negative correlation between the number of blood transfusions a patient had and their outcome (r = 0.605, P < 0.001) and death (r = 0.698, P < 0.001). CONCLUSION: A higher initial ICU APACHE II score, SOFA score, and a number of blood transfusions were associated with improved survival for patients undergoing major surgical operations. Patients' death rates have increased with the increase in the frequency and variety of blood transfusions.

Key Factors for Binders to Enhance the Electrochemical Performance of Silicon Anodes through Molecular Design.

Silicon is considered the most promising candidate for anode material in lithium-ion batteries due to the high theoretical capacity. Unfortunately, the vast volume change and low electric conductivity have limited the application of silicon anodes. In the silicon anode system, the binders are essential for mechanical and conductive integrity. However, there are few reviews to comprehensively introduce binders from the perspective of factors affecting performance and modification methods, which are crucial to the development of binders. In this review, several key factors that have great impact on binders' performance are summarized, including molecular weight, interfacial bonding, and molecular structure. Moreover, some commonly used modification methods for binders are also provided to control these influencing factors and obtain the binders with better performance. Finally, to overcome the existing problems and challenges about binders, several possible development directions of binders are suggested.

[Clinical features of children with coronavirus disease 2019 complicated by acute encephalitis and related research advances]. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå„¿ç«¥åˆå¹¶æ€¥æ€§è„‘ç‚Žçš„ä¸´åºŠç‰¹ç‚¹åŠç ”ç©¶è¿›å±•.

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic since the end of 2019. There is an increasing number of reports on nervous system symptoms, among which encephalitis is considered a serious neurological complication of COVID-19, but there are few reports of this complication in China. Acute encephalitis has severe symptoms. If it is not identified early and treated in time, the mortality is high and the prognosis is poor. During the current global epidemic, it is necessary to pay attention to the severe nervous system symptoms of COVID-19. Therefore, this article summarizes the clinical features of COVID-19 complicated by acute encephalitis through literature review and a detailed analysis of medical records, so as to provide a reference for clinicians to deal with the cases of COVID-19 complicated by acute encephalitis.

[Short-term persistent symptoms in preschool children with mild/common coronavirus disease 2019 caused by Omicron variant infection after discharge: a follow-up study]. / Omicronå˜å¼‚æ ªæ„ŸæŸ“çš„è½»åž‹/æ™®é€šåž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå­¦é¾„å‰å„¿ç«¥å‡ºé™¢åŽçŸ­æœŸç›¸å ³æŒç»­ç—‡çŠ¶çš„éšè®¿.

OBJECTIVES: To investigate the persistent symptoms in preschool children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a basis for developing follow-up plans after infection and reducing and preventing related symptoms after infection. METHODS: The children, aged 0-5 years, who had Omicron BA.2 infection and were discharged from the pediatric ward of Shanghai Renji Hospital South Branch from April 13 to May 8, 2022, were enrolled as subjects, and related demographic and clinical data were collected. The children were followed up from the time to SARS-CoV-2 clearance for two consecutive tests with an interval of >24 hours till 4-5 weeks after clearance, and telephone follow-up was performed on the primary caregivers to investigate related persistent symptoms. RESULTS: Among the 103 children who met the inclusion criteria, there were 61 boys and 42 girls, with a median age of 18 months. The primary caregivers who had received two or more doses of COVID-19 vaccine accounted for 64.1% (66/103). Fever (98.1%, 101/103) was the most common symptom in these children, followed by cough/expectoration (63.1%, 65/103), gastrointestinal problems (37.9%, 39/103), loss of appetite (30.1%, 31/103), weakness (27.2%, 28/103), and nasal obstruction/runny nose (16.5%, 17/103). The follow-up at 1 month after discharge reported that 44 children (42.7%) had at least one persistent symptom, including respiratory symptoms in 14 children (13.6%) and gastrointestinal problems in 19 children (18.4%). The children whose primary caregivers received two or more doses of COVID-19 vaccine had a significantly shorter time to SARS-CoV-2 clearance than those whose primary caregivers did not receive or only received one dose of COVID-19 vaccine (P<0.05), while there was no significant difference between the two groups in the proportion of children with at least one persistent symptom (P>0.05). CONCLUSIONS: Nearly half of the preschool children may have related persistent symptoms after SARS-CoV-2 Omicron variant infection, mainly gastrointestinal and respiratory symptoms. Most of the symptoms may be mild, and continuous follow-up is needed to observe their outcomes. Vaccination of COVID-19 vaccine for primary caregivers has a certain protective effect on children.

Management experience of a designated hospital for children with coronavirus disease 2019. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå„¿ç«¥å®šç‚¹åŒ»é™¢ç®¡ç†ç»éªŒåˆ†äº«.

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.

circRNAs Are Involved in the Rice-Magnaporthe oryzae Interaction.

Circular RNAs (circRNAs) play roles in various biological processes, but their functions in the rice (Oryza sativa) response to Magnaporthe oryzae remain elusive. Here, we demonstrate that circRNAs are involved in the rice-M. oryzae interaction using comparative circRNA-sequencing and transgenic approaches. We identified 2932 high-confidence circRNAs from young leaves of the blast-resistant accession International Rice Blast Line Pyricularia-Kanto51-m-Tsuyuake (IR25) and the blast-susceptible accession Lijiangxin Tuan Heigu (LTH) under M oryzae-infected or uninfected conditions; 636 were detected specifically upon M oryzae infection. The circRNAs in IR25 were significantly more diverse than those in LTH, especially under M. oryzae infection. Particularly, the number of circRNAs generated per parent gene was much higher in IR25 than in LTH and increased in IR25 but decreased in LTH upon M. oryzae infection. The higher diversity of circRNAs in IR25 was further associated with more frequent 3' and 5' alternative back-splicing and usage of complex splice sites. Moreover, a subset of circRNAs was differentially responsive to M oryzae in IR25 and LTH. We further confirmed that circR5g05160 promotes rice immunity against M oryzae Therefore, our data indicate that circRNA diversity is associated with different responses to M oryzae infection in rice and provide a starting point to investigate a new layer of regulation in the rice-M oryzae interaction.

Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling.

The mechanosensitive gene tenomodulin (Tnmd) is implicated in tendon maturation and repair. However, the mechanism by which mechanical loading regulates Tnmd's expression and its role in tenocyte migration is yet to be defined. Here, we show that Tnmd and migration were upregulated in uniaxial cyclic stress-stimulated tenocytes. The knockdown of Tnmd reduced cell migration in the presence and absence of mechanical loading, suggesting that Tnmd is involved in tenocyte migration. Moreover, the treatment of stress-stimulated tenocytes with the actin inhibitor latrunculin (Lat A), histone acetyltransferase inhibitor anacardic acid (ANA), or histone demethylases inhibitor GSK-J4 suppressed Tnmd expression and tenocyte migration. These results show that actin stress fiber formation and chromatin decondensation regulates Tnmd expression, which might then regulate tenocyte migration. Thus, this study proposes the involvement of the actin and chromatin mechanotransduction pathway in the regulation of Tnmd and reveals a novel role of Tnmd in tenocyte migration. The identification of Tnmd function in tenocyte migration provides insight into the molecular mechanisms involved in Tnmd-mediated tendon repair.

Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency.

Mutations in FASTKD2, a mitochondrial RNA binding protein, have been associated with mitochondrial encephalomyopathy with isolated complex IV deficiency. However, deficiencies related to other oxidative phosphorylation system (OXPHOS) complexes have not been reported. Here, we identified three novel FASTKD2 mutations, c.808_809insTTTCAGTTTTG, homoplasmic mutation c.868C>T, and heteroplasmic mutation c.1859delT/c.868C>T, in patients with mitochondrial encephalomyopathy. Cell-based complementation assay revealed that these three FASTKD2 mutations were pathogenic. Mitochondrial functional analysis revealed that mutations in FASTKD2 impaired the mitochondrial function in patient-derived lymphocytes due to the deficiency in multi-OXPHOS complexes, whereas mitochondrial complex II remained unaffected. Consistent results were also found in human primary muscle cell and zebrafish with knockdown of FASTKD2. Furthermore, we discovered that FASTKD2 mutation is not inherently associated with epileptic seizures, optic atrophy, and loss of visual function. Alternatively, a patient with FASTKD2 mutation can show sinus tachycardia and hypertrophic cardiomyopathy, which was partially confirmed in zebrafish with knockdown of FASTKD2. In conclusion, both in vivo and in vitro studies suggest that loss of function mutation in FASTKD2 is responsible for multi-OXPHOS complexes deficiency, and FASTKD2-associated mitochondrial disease has a high degree of clinical heterogenicity.

Aberrant Kank1 expression regulates YAP to promote apoptosis and inhibit proliferation in OSCC.

The kidney ankyrin repeat-containing protein 1 (Kank1) gene is one of the most important members of the KANK family. Kank1 has hybridity deletion and promoter methylation in the cancer tissues of the brain, lung, kidney and the corresponding cell lines, leading to downregulation of the gene expression. Meanwhile, Kank1 also plays a key role in the occurrence and development of various types of tumors, suggesting that Kank1 may be an anti-oncogene. However, its role and the potential mechanisms in the Oral Squamous Cell Carcinoma (OSCC) remain unclear. We examined the expression of Kank1 in OSCC tissues and explored its clinical significance. In addition, we investigated the effects of Kank1 on the biological behavior of OSCC cells and their specific molecular mechanisms. We found that Kank1 was poorly expressed in OSCC tissues and it is correlated with the OSCC stage and the patient's poor prognosis. By overexpression of Kank1, we found that the proliferation ability of the OSCC cells decreased both in vitro and in vivo, the proportion of apoptotic cells increased, and the mitochondrial transmembrane potential decreased. In terms of the molecular mechanism, we confirmed that Kank1 could inhibit the occurrence of OSCC by regulating Yap to inhibit the proliferation and promote apoptosis of the OSCC cells. Moreover, it was found that the overexpression of YAP reversed those effects caused by Kank1 overexpression on the OSCC cells. In conclusion, the research indicated that Kank1 might play an anti-oncogenic role in OSCC and it could be considered to be a target for the diagnosis and the treatment of OSCC.

Mutations in TOMM70 lead to multi-OXPHOS deficiencies and cause severe anemia, lactic acidosis, and developmental delay.

TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria. Here, we identified two compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)] from a patient with severe anemia, lactic acidosis, and developmental delay. Patient-derived immortalized lymphocytes showed decreased TOM70 expression, oligomerized TOM70 complex, and TOM 20/22/40 complex compared with expression in control lymphocytes. Functional analysis revealed that patient-derived cells exhibited multi-oxidative phosphorylation system (OXPHOS) complex defects, with complex IV being primarily affected. As a result, patient-derived cells grew slower in galactose medium and generated less ATP and more extracellular lactic acid than did control cells. In vitro cell model compensatory experiments confirmed the pathogenicity of TOMM70 variants since only wild-type TOM70, but not mutant TOM70, could restore the complex IV defect and TOM70 expression in TOM70 knockdown U2OS cells. Altogether, we report the first case of mitochondrial disease-causing mutations in TOMM70 and demonstrate that TOM70 is essential for multi-OXPHOS assembly. Mutational screening of TOMM70 should be employed to identify mitochondrial disease-causing gene mutations in the future.

Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis.

BACKGROUND: Increasing studies have demonstrated that long non-coding RNAs (lncRNAs) play an important role in tumor progression. However, the potential biological functions and clinical importance of Linc01234 in oral squamous cell carcinoma (OSCC) remain unclear. METHODS: We evaluated the expression profile and prognostic value of Linc01234 in OSCC tissues by RT-qPCR. Then, functional in vitro experiments were performed to investigate the effects of Linc01234 on tumor growth, migration and invasion in OSCC. Mechanistically, RT-qPCR, bioinformatic analysis and dual luciferase reporter assays were performed to identify a competitive endogenous RNA (ceRNA) mechanism involving Linc01234, miR-433-3p and PAK4. RESULTS: We found that Linc01234 was clearly upregulated in OSCC tissues and cell lines, and its level was positively associated with T stage, lymph node metastasis, differentiation and poor prognosis of patients with OSCC. Our results shown that Linc01234 inhibited cell proliferation and metastatic abilities in CAL27 and SCC25 cells following its knockdown. Mechanistic analysis indicated that Linc01234 may act as a ceRNA (competing endogenous RNA) of miR-433-3p to relieve the repressive effect of miR-433-3p on its target PAK4. CONCLUSIONS: Our results indicated that Linc01234 promotes OSCC progression through the Linc01234/miR-433/PAK4 axis and might be a potential therapeutic target for OSCC.

A novel mitochondrial m.14430A>G (MT-ND6, p.W82R) variant causes complex I deficiency and mitochondrial Leigh syndrome.

Objectives Leigh syndrome (LS) is one of the most common mitochondrial diseases and has variable clinical symptoms. However, the genetic variant spectrum of this disease is incomplete. Methods Next-generation sequencing (NGS) was used to identify the m.14430A > G (p.W82R) variant in a patient with LS. The pathogenesis of this novel complex I (CI) variant was verified by determining the mitochondrial respiration, assembly of CI, ATP, MMP and lactate production, and cell growth rate in cybrids with and without this variant. Results A novel m.14430A > G (p.W82R) variant in the NADH dehydrogenase 6 (ND6) gene was identified in the patient; the mutant loads of m.14430A > G (p.W82R) in the patient were much higher than those in his mother. Although the transmitochondrial cybrid-based study showed that mitochondrial CI assembly remains unaffected in cells with the m.14430G variant, control cells had significantly higher endogenous and CI-dependent mitochondrial respiration than mutant cells. Accordingly, mutant cells had a lower ATP, MMP and higher extracellular lactate production than control cells. Notably, mutant cells had impaired growth in a galactose-containing medium when compared to wild-type cells. Conclusions A novel m.14430A > G (p.W82R) variant in the ND6 gene was identified from a patient suspected to have LS, and this variant impaired mitochondrial respiration by decreasing the activity of mitochondrial CI.

Osa-miR1873 fine-tunes rice immunity against Magnaporthe oryzae and yield traits.

MicroRNAs (miRNAs) are known to fine-tune growth, development, and stress-induced responses. Osa-miR1873 is a rice-specific miRNA targeting LOC_Os05g01790. Here, we show that Osa-miR1873 fine-tunes rice immunity against Magnaporthe oryzae and yield traits via LOC_Os05g01790. Osa-miR1873 was significantly upregulated in a susceptible accession but downregulated in a resistance accession at 24 h post-inoculation (hpi) of M. oryzae. Overexpressing Osa-miR1873 enhanced susceptibility to M. oryzae and compromised induction of defense responses. In contrast, blocking Osa-miR1873 through target mimicry compromised susceptibility to M. oryzae and enhanced induction of defense responses. Altered expression of Osa-miR1873 also resulted in some defects in yield traits, including grain numbers and seed setting rate. Moreover, overexpression of the target gene LOC_Os05g01790 increased rice blast disease resistance but severely penalized growth and yield. Taken together, we demonstrate that Osa-miR1873 fine-tunes the rice immunity-growth trade-off via LOC_Os05g01790, and blocking Osa-miR1873 could improve blast disease resistance without significant yield penalty. Thus, the Osa-miR1873-LOC_Os05g01790 regulatory module is valuable in balancing yield traits and blast resistance.

In vivo study on the repairment of distal femur defects in rabbit with nano-pearl powder bone substitute. / çº³ç±³çç ç²‰äººå·¥éª¨ä¿®å¤å ”è‚¡éª¨è¿œç«¯ç¼ºæŸ.

OBJECTIVES: To evaluate the repairing ability of nano-pearl powder bone substitute in rabbit with defect of distal femur bone. METHODS: Thirty-two New Zealand rabbits were randomly divided into four groups: a nano-pearl powder/recombinant human bone morphogenetic protein 2 (rhBMP-2)/hyaluronic acid group, a nano-pearl powder/hyaluronic acid group, a nano-pearl powder group and a blank control group (n=8 in each group). A defect with the diameter of 7 mm and height of 10 mm was prepared at the distal femoral metaphysis line of the rabbit.Different bone substitutes were planted, and the effect of repair was evaluated by macroscopic observation, imaging examination, and histopathological examination. RESULTS: The results of imageology showed that: the bone repairing effect in the nano-pearl powder/rhBMP-2/hyaluronic acid group was better than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group, and which in the 3 experimental groups was better than that in the blank control group; The results of histology showed that: at the 4th, 8th and 12th weeks after the modeling operation, the speed of bone repair in the nano-pearl powder/rhBMP-2/hyaluronic acid group was faster than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group, and which in the blank control group was far slower than that in the 3 experimental groups. The results of immunohistochemistry staining for osteocalcin antibody showed that: the osteogenic effect in the nano-pearl powder/rhBMP-2/hyaluronic acid group was better than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group (both P<0.05); there was no significant difference between the nano-pearl powder/hyaluronic acid group and the pure pearl powder group (P>0.05); however, there was significant difference between the pure pearl powder group and the blank control group (P<0.05). According to the staining results of Type I collagen antibody, there was no significant difference in the osteogenic effect between the nano-pearl powder/rhBMP-2/hyaluronic acid group and the nano-pearl powder/hyaluronic acid group (P>0.05), but the osteogenic effect in the nano-pearl powder/hyaluronic acid group was better than that in the pure pearl powder group and the blank control group (both P<0.05). CONCLUSIONS: Nano-pearl powder and its bone substitute can promote the repair of bone defect, and the nano-pearl powder which contains rhBMP-2 has better osteogenic and repairing effect on defect.

Investigation of Drug for Pulmonary Administration-Model Pulmonary Surfactant Monolayer Interactions Using Langmuir-Blodgett Monolayer and Molecular Dynamics Simulation: A Case Study of Ketoprofen.

Pulmonary administration is widely used for the treatment of lung diseases. The interaction between drug molecules and pulmonary surfactants affects the efficacy of the drug directly. The location and distribution of drug molecules in a model pulmonary surfactant monolayer under different surface pressures can provide vivid information on the interaction between drug molecules and pulmonary surfactants during the pulmonary administration. Ketoprofen is a nonsteroidal anti-inflammatory drug for pulmonary administration. The effect of ketoprofen molecules on the lipid monolayer containing 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-glycerol (DPPG) is studied by surface pressure (π)-area (A) isotherms and compressibility modulus (Cs-1)-surface pressure (π) isotherms. The location and distribution of ketoprofen molecules in a lipid monolayer under different surface pressures are explored by surface tension, density profile, radial distribution function (RDF), and the potential of mean force (PMF) simulated by molecular dynamics (MD) simulation. The introduction of ketoprofen molecules affects the properties of DPPC/DPPG monolayers and the location and distribution of ketoprofen molecules in monolayers with various surface pressures. The existence of ketoprofen molecules hinders the formation of liquid-condensed (LC) films and decreases the compressibility of DPPC/DPPG monolayers. The location and distribution of ketoprofen molecules in the lipid monolayer are affected by cation-π interaction between the choline group of lipids and the benzene ring of ketoprofen, the steric hindrance of the lipid head groups, and the hydrophobicity of ketoprofen molecule itself, comprehensively. The contact state of lipid head group with water is determined by surface pressure, which affects the interaction between drug molecules and lipids and further dominates the location and distribution of ketoprofen in the lipid monolayer. This work confirms that ketoprofen molecules can affect the property and the inner structure of DPPC/DPPG monolayers during breathing. Furthermore, the results obtained using a mixed monolayer containing two major pulmonary surfactants DPPC/DPPG and ketoprofen molecules will be helpful for the in-depth understanding of the mechanism of inhaled administration therapy.