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Plants frequently evade extreme environmental stress by initiating early flowering, yet the underlying mechanisms remain incompletely understood. Here, through extensive mutant screening, we identify a vegetative growth to reproductive growth transition factor (vrf1) mutant, which exhibits a deficiency in drought escape. Alternative splicing of VRF1 generates four isoforms, of which two encode functional proteins, VRF1-AS1 and VRF1-AS3. The proportions of VRF1-AS1 and VRF1-AS3 are modulated by environmental factors, serving as a molecular switch mediating the transition from tolerance to early flowering, irrespective of their absolute abundance. VRF1-AS1 and VRF1-AS3 competitively bind to MKK1, resulting in MKK1 phosphorylation at different sites, which opens two distinct regulatory pathways. The role of VRF1 is conserved across various conditions, and 66 Arabidopsis ecotypes suggest its central function in stress avoidance through premature flowering. In summary, our findings show that plants respond precisely and effectively to dynamic environmental changes by modulating their isoform ratios., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Intracellular trafficking, an extremely complex network, dynamically orchestrates nearly all cellular activities. A versatile method that enables the manipulation of target transport pathways with high spatiotemporal accuracy in vitro and in vivo is required to study how this network coordinates its functions. Here, a new method called RIVET (Rapid Immobilization of target Vesicles on Engaged Tracks) is presented. Utilizing inducible dimerization between target vesicles and selective cytoskeletons, RIVET can spatiotemporally halt numerous intracellular trafficking pathways within seconds in a reversible manner. Its highly specific perturbations allow for the real-time dissection of the dynamic relationships among different trafficking pathways. Moreover, RIVET is capable of inhibiting receptor-mediated endocytosis. This versatile system can be applied from the cellular level to whole organisms. RIVET opens up new avenues for studying intracellular trafficking under various physiological and pathological conditions and offers potential strategies for treating trafficking-related disorders., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Multi-organ metastasis has been the main cause of death in patients with Gastric cancer (GC). The prognosis for patients with metastasized GC is still very poor. Long noncoding RNAs (lncRNAs) always been reported to be closely related to cancer metastasis., Methods: In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected by Transwell, Wound healing, Western Blot or other assays in vitro and in vivo . Further mechanism study was performed by RNA FISH, Dual-luciferase reporter assay and RT-qPCR. Finally, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 in patient tissues was detected by RT-qPCR., Results: In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected in vitro and in vivo . The results shown that overexpression of the lncRNA CADM2-AS1 promoted GC metastasis, while knockdown inhibited it. Further mechanism study proved that lncRNA CADM2-AS1 could sponge and silence miR-5047, which targeting mRNA was NOTCH4. Elevated expression of lncRNA CADM2-AS1 facilitate GC metastasis by up-regulating NOTCH4 mRNA level consequently. What's more, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 was further detected and verified in metastatic GC patient tissues., Conclusions: LncRNA CADM2-AS1 promoted metastasis in GC by targeting the miR-5047/NOTCH4 signaling axis, which may be a potential target for GC metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhao, Zhou, Zhao, Geng, Zhang, Sun and Chen.)

Objective: To analyze the disease characteristics, diagnosis and treatment methods of venous pulsatile tinnitus treated by intervention of sigmoid sinus. Methods: Fifty patients (from Shandong Provincial ENT Hospital, Shandong University between February 2014 and July 2020) with venous pulsatile tinnitus treated by sigmoid sinus surgery were analyzed retrospectively. The tinnitus characteristics, imaging findings, surgical methods, intraoperative findings and postoperative tinnitus changes were recorded. The patients were followed up for 6-12 months. The sign rank sum test was used to analyze the difference in tinnitus grading before and after surgery. There were 50 patients with unilateral venous pulsatile tinnitus, including 49 females and 1 male. The age ranged from 17 to 67 years, with a median age of 44 years. There were 45 cases of right tinnitus and 5 cases of left tinnitus. The degree of tinnitus before operation was grade Ⅱ or above, including 4 cases of gradeⅡ, 11 cases of grade Ⅲ, 22 cases of grade Ⅳ and 13 cases of grade Ⅴ. Results: Thirty-seven cases were cured, 8 cases were ineffective (no change in tinnitus), 3 cases were markedly effective (tinnitus grade decreased by 3 in 2 cases, 4 in 1 case), and 2 cases were effective (tinnitus grade decreased by 1). The difference of tinnitus grade before and after operation was statistically significant ( Z =-5.70, P <0.05). Temporal bone CT showed 36 cases of sigmoid diverticulum (including 17 cases with sigmoid sinus dehiscence), 12 cases of sigmoid sinus dehiscence and 2 cases of absence of the temporal bone cortex abutting to sigmoid sinus. Thirty-five cases were performed with closure of sigmoid sinus diverticulum, 4 cases were performed with resurfacing of the sigmoid plate, 5 cases were performed with narrowing of sigmoid sinus, 4 cases were performed with simple opening of pre sigmoid mastoid air chamber, 1 case of opening was performed with pre sigmoid mastoid air chamber combined with narrowing of sigmoid sinus, and 1 case was performed with opening of pre sigmoid mastoid air chamber combined with closure of sigmoid sinus diverticulum. Conclusions: Venous pulsatile tinnitus is common in women. The common causes may be sigmoid sinus wall abnormalities such as sigmoid sinus diverticulum and perisigmoid bone defect. Imaging examinations are helpful for diagnosis. Venous pulsatile tinnitus can be treated with surgery.

This study investigated the benefits and challenges of intergenerational tutoring in a post-pandemic context. We explored how the benefits of intergenerational tutoring vary among subgroups of volunteers-first-time tutors, male tutors, tutors who are caregivers, and tutors with moderate or severe loneliness. Older adult tutors ( N = 319) were surveyed before and after the 2021-2022 school year, and the data were analyzed with structural equation multivariate regression and thematic analysis. Results indicated that while public health measures like mask-wearing posed challenges for some tutors, there were positive outcomes for tutors, especially first-time tutors, who experienced more health and well-being benefits, and tutors who are caregivers, who experienced improved civic attitudes towards public education. These results can help programs attract subgroups of volunteers who are likely to benefit the most, as well as attend to the unique challenges of pandemic-related policies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Home- and community-based services (HCBS) help older adults to remain active in community settings. However, it is not known if there is a causal relationship between HCBS and social engagement. Methods: We used data from the 2010 and 2012 Health and Retirement Study and measured the effect of HCBS on social engagement via nearest-neighbor Mahalanobis matching, optimal pair matching, genetic matching, and optimal full matching. Results: Genetic matching showed that the odds of social engagement for participants who received at least one HCBS (congregate meal, home-delivered meal, transportation service, case management, homemaker or housekeeping services, or caregiver services) in the prior two years was 1.07 times more likely than participants who have not received any HCBS (robust SE = .030, p = .040). Discussion: HCBS may remove barriers to social engagement through increasing older adults' personal resources and personal networks., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Inadequate response to balance perturbations lead to posture instability in the elderly. The fall risks are increased by a reduced capacity to control the center of pressure (COP) displacement within the safety limit of the supporting base. This study developed an interactive evaluation and training platform. The system incorporated a computerized program with instantaneous force plate evaluation. Ten young subjects underwent a baseline evaluation and twenty-nine community-dwelling elderly received pre- and post-intervention testing. The ability to reach the stability limit was assessed by measuring the maximum voluntary excursion of the COP in anterior-posterior and medial-lateral directions. Functional mobility tests including Berg Balance Scale, Timed-Up-and-Go and functional reach were used as functional outcomes. The experimental group ( n = 15) received a 40 min intervention three times a week for six weeks. The interactive game-based training focused on multi-directional weight shifting by tracing a COPcontrolled target to challenge an individual's stability limit. The control group ( n = 14) maintained daily activities as usual. The young group revealed a superior COP displacement through active ankle control than the elderly, especially in the anterior-posterior direction. The experimental group improved their COP displacement control more in the medial-lateral direction due to the predominant side-to-side gameplay movement. The functional outcome measures were also significantly improved after training. Using the COPcontrolled game-based program, the stability limit was challenged to facilitate dynamic posture control by an incremental increase in self-initiated perturbations. The platform system could assist in transferring the immediate training effects into daily functional mobility in the elderly.

Most polycyclic aromatic hydrocarbons (PAHs), which are persistent organic pollutants, have strong carcinogenicity, teratogenicity, and mutagenicity, and pose serious threats to the ecological environment and human health. Owing to the complexity of the matrix and low PAH content of environmental samples, separating and enriching PAHs in environmental samples is necessary prior to their detection. Solid-phase microextraction (SPME) technology is commonly used to detect PAHs owing to its advantages of simple operation, online connection with other instruments, low solvent usage, and integrability of sampling separation, enrichment, and desorption. The extraction coating is the core of this technology, and the type and thickness of the coating are important factors affecting the sensitivity and accuracy of the analysis. Common commercial extraction coatings include polydimethylsiloxane and quartz fiber; however, these materials have a number of disadvantages, such as poor thermal stability and high cost. Several methods, including electrochemical, sol-gel, molecular imprinting, and other coating methods, have been developed to prepare SPME coatings. Electrochemical methods have attracted considerable attention because of their simplicity, short duration, and high coating stability. In the development of an electrochemical method, the selection of the conductive polymer is of particular importance. Polypyrroles (Ppy) are easily synthesized and have numerous advantages, such as good conductivity and stable chemical properties. Thus, their use as a substrate material for SPME coatings is beneficial for improving the overall stability of the coating. Copolymerization with other polymers can enhance the adsorption performance of such coatings via synergistic effects. When doped with inorganic materials with high thermal stability, the composite coating can exhibit high temperature resistance. In this study, a porous boron nitride-doped Ppy-2,3,3-trimethylindole (Ppy/P2,3,3-TMe@In/BN) composite was prepared as a new SPME copolymer coating to detect three PAHs: naphthalene (NAP), acenaphthene (ANY), and fluorene (FLU). Scanning electron microscopy, thermal stability analysis, Fourier transform infrared spectroscopy, and other techniques were used to characterize the Ppy/P2,3,3-TMe@In/BN composite coating. The results showed that the coating featured a large number of porous and wrinkled dendritic structures, which increased the specific surface area of the composite coating and enabled the extensive enrichment of the three PAHs. When the sample inlet temperature of the chromatograph is 320 ℃, the chromatographic baseline of the coating is basically stable. Compared with commercial coatings, the prepared coating had better thermal stability. The coating formed stable intermolecular forces with the three PAHs owing to its numerous carbon-carbon double bonds (C=C), hydrogen bonds, and other structures, thereby achieving excellent enrichment of the target analytes. Compared with Ppy, Ppy/PIn, Ppy/P2,3,3-TMe@In, Ppy/BN, and polydimethylsiloxane (PDMS) coatings, the prepared Ppy/P2,3,3-TMe@In/BN composite coating exhibited better extraction effects for the three PAHs. The Ppy/P2,3,3-TMe@In/BN composite coating was polymerized on the surface of a stainless-steel wire by cyclic voltammetry and combined with gas chromatography-hydrogen flame ionization detection (GC-FID) to optimize the conditions influencing the extraction and separation of the three PAHs, thereby establishing a highly sensitive analytical method for detecting NAP, ANY, and FLU. This method had low limits of detection (LODs) of 10.6-14.5 ng/L ( S/N =3) and high stability. The SPME-GC-FID method was used to detect the three PAHs in two environmental water samples, and a small amount of ANY (1.39 μg/L) was detected in one water sample. Satisfactory recoveries (82.5%-113.9%) were obtained when both water samples were spiked with the three PAHs at three levels. The experimental results indicate that the established analytical method can detect the three PAHs in environmental water samples.

This study explored the experiences of older adult volunteers who pivoted from in-person tutoring to letter writing and online tutoring during the COVID-19 pandemic. Sixty-one older adult volunteers were surveyed in the beginning and end of the school year about their experiences, including their perceived benefits, challenges, and feedback on the pandemic transition. Eleven of the surveyed volunteers participated in focus groups at the end of the school year. Perceived benefits included having a positive impact on a child's life and meaningful engagement during the pandemic, and perceived challenges included difficulty engaging students and lack of control over learning environments. The participants also suggested increasing opportunities for informal interactions with staff and students, technology training, and peer support between volunteers. There was agreement that the remote volunteering experience was not a substitute for in-person tutoring, but it was better than no volunteering at all.

Recent declines in life expectancy in the US, especially for middle-aged White persons, have called attention to mortality from deaths of despair - deaths due to alcohol, drugs, and suicide. Using data from the Centers for Disease Control and the U.S. Census Bureau, this paper examined deaths of despair by race/ethnicity, age, cause of death, birth cohort, and sex in Missouri. We focused on Area Agencies on Aging as geographic units of interest to increase usefulness of our findings to public administrators. Deaths of despair began trending up for all age groups beginning in 2007-2009, with the sharpest increases occurring for Black or African American non-Hispanics beginning in 2013-2015. The most dramatic increases occurred for the population age 50-59 in St. Louis City and Area Agency on Aging regions in southern Missouri. For older adults, considerable variation in rates, trends, and cause of deaths of despair is evident across the state.

Microangiopathy should be noted in diabetes with subclinical vascular diseases. Little is known about whether various surrogate markers of systemic arterial trees exacerbate simultaneously in preclinical atherosclerosis. To clarify the association of skin microvascular reactivity with arterial stiffness is essential to elucidating early atherosclerotic changes. The post-occlusive reactive hyperemia of skin microcirculation was evaluated in 27 control and 65 type 2 diabetic subjects, including 31 microalbuminuria (MAU) and 34 normoalbuminuria (NAU) patients. The laser Doppler skin perfusion signals were transformed into three frequency intervals for the investigation of endothelial, neurogenic, and myogenic effects on basal and reactive flow motion changes. The analysis of spectral intensity and distribution provided insight into potential significance of microvascular regulation in subclinical atherosclerotic diseases. Systemic arterial stiffness was studied by the brachial ankle pulse wave velocity (baPWV). Following occlusive ischemia, the percent change of endothelial flow motion was lower in MAU than in NAU and control groups. The MAU group revealed a relative increase in myogenic activity and a decrease in endothelial activity in normalized spectra. The baPWV showed more significant associations with reactive endothelial change (r = - 0.48, P < 0.01) and normalized myogenic value (r = - 0.37, P < 0.05) than diabetes duration and HbA1c. By multivariate regression analysis, only endothelial vasomotor changes independently contributed to the decreased baPWV (OR 3.47, 95% CI 1.63-7.42, P < 0.05). Impaired microcirculatory control is associated with increased arterial stiffness in preclinical atherosclerosis. To identify the early manifestations is necessary for at-risk patients to prevent from further vascular damage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

It has been shown that several ribonuclease (RNase) A superfamily proteins serve as ligands of receptor tyrosine kinases (RTKs), representing a new concept for ligand/receptor interaction. Moreover, recent studies indicate high clinical values for this type of ligand/RTK interactions. However, there is no structural report for this new family of ligand/receptor. In an attempt to understand how RNase and RTK may interact, we focused on the RNase1/ephrin type-A receptor 4 (EphA4) complex and predicted their structure by using the state-of-the-art machine learning method, AlphaFold and its derivative method, AF2Complex. In this model, electrostatic force plays an essential role for the specific ligand/receptor interaction. We found the R39 of RNase1 is the key residue for EphA4-binding and activation. Mutation on this residue causes disruption of an essential basic patch, resulting in weaker ligand-receptor association and leading to the loss of activation. By comparing the surface charge distribution of the RNase A superfamily, we found the positively charged residues on the RNase1 surface is more accessible for EphA4 forming salt bridges than other RNases. Furthermore, RNase1 binds to the ligand-binding domain (LBD) of EphA4, which is responsible for the traditional ligand ephrin-binding. Our model reveals the location of RNase1 on EphA4 partially overlaps with that of ephrin-A5, a traditional ligand of EphA4, suggesting steric hindrance as the basis by which the ephrin-A5 precludes interactions of RNase1 with EphA4. Together, our discovery of RNase1/EphA4 interface provides a potential treatment strategy by blocking the RNase1-EphA4 axis., Competing Interests: None., (AJCR Copyright © 2022.)

Microtubules tightly regulate various cellular activities. Our understanding of microtubules is largely based on experiments using microtubule-targeting agents, which, however, are insufficient to dissect the dynamic mechanisms of specific microtubule populations, due to their slow effects on the entire pool of microtubules. To overcome this technological limitation, we have used chemo and optogenetics to disassemble specific microtubule subtypes, including tyrosinated microtubules, primary cilia, mitotic spindles, and intercellular bridges, by rapidly recruiting engineered microtubule-cleaving enzymes onto target microtubules in a reversible manner. Using this approach, we show that acute microtubule disassembly swiftly halts vesicular trafficking and lysosomal dynamics. It also immediately triggers Golgi and ER reorganization and slows the fusion/fission of mitochondria without affecting mitochondrial membrane potential. In addition, cell rigidity is increased after microtubule disruption owing to increased contractile stress fibers. Microtubule disruption furthermore prevents cell division, but does not cause cell death during interphase. Overall, the reported tools facilitate detailed analysis of how microtubules precisely regulate cellular architecture and functions., (© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Background: Helicobacter pylori ( H. pylori ) has characteristics of family cluster infection; however, its family-based infection status, related factors, and transmission pattern in central China, a high-risk area for H. pylori infection and gastric cancer, have not been evaluated. We investigated family-based H. pylori infection in healthy households to understand its infection status, related factors, and patterns of transmission for related disease prevention., Aim: To investigate family-based H. pylori infection status, related factors, and patterns of transmission in healthy households for related disease prevention., Methods: Blood samples and survey questionnaires were collected from 282 families including 772 individuals. The recruited families were from 10 selected communities in the greater Zhengzhou area with different living standards, and the family members' general data, H. pylori infection status, related factors, and transmission pattern were analyzed. H. pylori infection was confirmed primarily by serum H. pylori antibody arrays; if patients previously underwent H. pylori eradication therapy, an additional 13 C-urea breath test was performed to obtain their current infection status. Serum gastrin and pepsinogens (PGs) were also analyzed., Results: Among the 772 individuals examined, H. pylori infection rate was 54.27%. These infected individuals were from 246 families, accounting for 87.23% of all 282 families examined, and 34.55% of these families were infected by the same strains. In 27.24% of infected families, all members were infected, and 68.66% of them were infected with type I strains. Among the 244 families that included both husband and wife, spouse co-infection rate was 34.84%, and in only 17.21% of these spouses, none were infected. The infection rate increased with duration of marriage, but annual household income, history of smoking, history of alcohol consumption, dining location, presence of gastrointestinal symptoms, and family history of gastric disease or GC did not affect infection rates; however, individuals who had a higher education level showed lower infection rates. The levels of gastrin-17, PGI, and PGII were significantly higher, and PGI/II ratio was significantly lower in H. pylori -infected groups than in H. pylori -negative groups., Conclusion: In our study sample from the general public of central China, H. pylori infection rate was 54.27%, but in 87.23% of healthy households, there was at least 1 H. pylori -infected person; in 27.24% of these infected families, all members were infected. Type I H. pylori was the dominant strain in this area. Individuals with a higher education level showed significantly lower infection rates; no other variables affected infection rates., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the clinical features, pathological types, imaging features, and surgical strategies of lateral skull base benign tumors with intracranial invasion. Methods: From January 2011 to March 2021, 36 patients of lateral skull base benign tumors with intracranial invasion were included in this retrospective study. Among the 36 patients, 14 cases were male, 22 cases were female, the aged range from 20-67, with the median age of 48. The clinical manifestations, characteristic imaging findings, pathological types, surgical approach selection, and prognosis were analyzed. Results: 36 cases of lateral skull base tumors with intracranial invasion were all accepted surgeries. 23 cases were neurogenic tumors, facial nerve tumors ( n =8), neurogenic tumors in jugular foramen with unknown origin( n =6), hypoglossal schwannoma ( n =3), transotic intralabyrinthine schwannoma ( n =3), vestibular schwannoma involving the middle ear( n =2), vagal nerve schwannoma( n =1). Other types of tumors included meningioma ( n =10) and paraganglioma (Di 1 or 2, n =3). Different pathological types of tumors had different clinical manifestations and imaging manifestations. Sixteen cases were subjected to primary resection, while, other 20 cases underwent staged operation. Among the patients with staged operation, 10 patients had completed the second stage operation, five patients were waiting for the second stage operation, the other five patient's residual intracranial tumor were significantly reduced and the space between tumor and brain tissues widened after the first stage operation, so, the following up with "wait and scan"policy was suggested. The total resection rate of tumors was related to the pathological nature, in which neurogenic tumors were 15/17, and meningiomas were 5/8. The main postoperative complications were cerebrospinal fluid leakage and infection in the operation area. There were two cases of postoperative intracranial infection, and three cases of cerebrospinal fluid leakage occurred in non staged operation cases. Conclusions: Lateral skull base tumors with intracranial invasion are rare. The most common pathological type is schwannoma, followed by meningioma and paraganglioma. For this type of tumor, if there is infection in the operation area and neck invasion is large, it is suggested to choose staged surgery, which can reduce the risk of intracranial infection and the incidence of cerebrospinal fluid leakage. Staged surgery strategy can also reduce the difficulty of second stage surgery, so the operation is much safer than non staged surgery.

Patients with chronic stroke often have difficulty opening their hands and performing grasping movements. Several passive hand orthoses for assisting hand rehabilitation have been developed and demonstrated to be clinically effective. However, current devices have several limitations, such as supporting only a single grasping motion and using an abnormal grasping posture. Therefore, this study developed a three-dimensional (3D)-printed multifunctional hand device (3DP-MFHD) to solve these problems and evaluated the feasibility of using the device during home rehabilitation. Six participants were enrolled, and each of them was provided with the 3DP-MFHD. In addition to a task-oriented training course, the participants were asked to train at home for 4 weeks for at least 5 days per week and 40 min per day. The results revealed that hand grip force increased by 36.1%, lateral pinch force increased by 17.6%, and the Action Research Arm Test score increased by 54.1%. The 3DP-MFHD is a promising means to facilitate hand rehabilitation and improve hand strength and function in patients with chronic stroke. The 3DP-MFHD can be used as part of home rehabilitation.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC 50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity., (© 2021. The Author(s).)

This study explored older adults' technology use patterns and attitudes toward virtual volunteering during the COVID-19 pandemic. A 22-item survey was administered to 229 volunteers in the St. Louis region who tutor children through the Oasis Intergenerational Tutoring program. Although most respondents are familiar with technology and expressed that they are likely to volunteer virtually, their responses varied significantly by age, education, gender, income, and school districts. Some tutors expressed that virtual volunteering may eliminate barriers to in-person volunteering, while others were concerned with establishing a personal connection with students online. These findings suggest that tutors anticipate both benefits and challenges with virtual volunteering and that efforts to engage older adults during the pandemic should factor in prior use of technology and ensure that different subgroups are not marginalized.

Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) is rapidly produced under proinflammatory stimuli, thereby feeding back to downregulate excessive inflammation. In this study, we used the stable, inducible expressions of wild-type (WT) MCPIP1 and an MCPIP1-D141N mutant in T-REx-293 cells by means of a tetracycline on (Tet-on) system. We found that WT MCPIP1 but not MCPIP1-D141N mutant expression dramatically increased apoptosis, caspase-3, -7, -8, and -9 activation, and c-Jun N-terminal kinase (JNK) phosphorylation in TNF-α-treated cells. The pan-caspase inhibitor, z-VAD-fmk, and the caspase-1 inhibitor, z-YVAD-fmk, but not the JNK inhibitor, SP600125, significantly reversed apoptosis and caspase activation in TNF-α/MCPIP1-treated cells. Surprisingly, MCPIP1 itself was also cleaved, and the cleavage was suppressed by treatment with the pan-caspase inhibitor and caspase-1 inhibitor. Moreover, MCPIP1 was found to contain a caspase-1/-4 consensus recognition sequence located in residues 234~238. As expected, the WT MCPIP1 but not the MCPIP1-D141N mutant suppressed NF-κB activation, as evidenced by inhibition of IκB kinase (IKK) phosphorylation and IκB degradation using Western blotting, IKK activity using in vitro kinase activity, and NF-κB translocation to nuclei using an immunofluorescence assay. Interestingly, MCPIP1 also significantly inhibited importin α3 and importin α4 expressions, which are major nuclear transporter receptors for NF-κB. Inhibition of NF-κB activation further downregulated expression of the caspase-8 inhibitor, cFLIP. In summary, the results suggest that MCPIP1 could enhance the TNF-α-induced apoptotic pathway through decreasing NF-κB activation and cFLIP expression.

Objective: Anatomic variations in the perigastric vessels during laparoscopic radical gastrectomy often affect the operator's judgment and prolong the operation time, and even cause accidental injury and surgical complications, and hence the safety and quality of the operation cannot be ensured. In this study, multiple slice CT was reconstructed by 3-dimensional CT simulation software (3D-CT), and 3D-CT images were used to describe the variation of celiac trunk and splenic artery before surgery. The guiding role of the different variation of vessels was analyzed for laparoscopic total gastrectomy+D2 lymph node dissection (LTG+D2LD). Methods: A retrospective cohort study was conducted. Case inclusion criteria: (1) Gastric cancer was at an advanced stage. All the patients were preoperatively examined by digestive endoscopy and 64-row enhanced CT scan, and were histopathologically diagnosed with gastric adenocarcinoma. (2) 3D-CT simulation images were reconstructed to guide the operation. (3) LTG+D2LD surgery was performed by the same surgical team. (4) Clinical data were complete, and all the patients had signed the informed consent. From 2014 to 2018, 98 patients with gastric cancer at the Gastrointestinal Surgery Department of Henan Provincial People's Hospital were enrolled. According to the Adachi classification, celiac trunk variation was divided into common type (Adachi type I) and rare type (Adachi type II-VI). According to the Natsume classification, splenic artery was classified into "flat type" and "curved type". Based on 3D-CT simulation images, variation of celiac trunk and splenic artery was described, and the differences in operation time, intraoperative blood loss and the number of postoperative retrieved lymph nodes were compared between groups with different types of arterial variation. Results: For celiac trunk, common type was found in 84 cases (86%) and rare type was found in 14 cases, including 6 cases (6%) of type II, 2 cases (2%) of type III, 2 cases (2%) of type IV, 3 cases (3%) of type V, 1 case (1%) of type VI. No other types were found. There were no statistically significant differences in clinical characteristics and number of retrieved lymph nodes between patients of the common type group and rare type group (all P >0.05). Compared with common type patients, those of rare type had longer operative time [(321.1±29.0) minutes vs. (295.1±46.5) minutes, t =2.081, P =0.040] and more intraoperative blood loss (median: 66.0 ml vs. 32.0 ml, Z =-4.974, P =0.001). For splenic artery, 41 patients (42%) were flat type and 57 patients (58%) were curved type. There were no statistically significant differences between the two groups in terms of clinical characteristics, intraoperative blood loss, operative time and number of retrieved lymph nodes (all P >0.05). Conclusions: The method of describing the variation in the perigastric vessels by 3D-CT simulation has certain clinical value in laparoscopic radical gastrectomy. The duration of LTG+D2LD is prolonged and the intraoperative blood loss is increased with the variation of celiac trunk, while the variation of splenic artery has no effect on LTG+D2LD.

Germination is a plant developmental process by which radicle of mature seeds start to penetrate surrounding barriers for seedling establishment and multiple environmental factors have been shown to affect it. Little is known how high salinity affects seed germination of C4 plant, Zea mays. Preliminary germination assay suggested that isolated embryo alone was able to germinate under 200 mM NaCl treatment, whereas the intact seeds were highly repressed. We hypothesized that maize endosperm may function in perception and transduction of salt signal to surrounding tissues such as embryo, showing a completely different response to that in Arabidopsis. Since salt response involves ABA, we analysed in vivo ABA distribution and quantity and the result demonstrated that ABA level in isolated embryo under NaCl treatment failed to increase in comparison with the water control, suggesting that the elevation of ABA level is an endosperm dependent process. Subsequently, by using advanced profiling techniques such as RNA sequencing and SWATH-MS-based quantitative proteomics, we found substantial differences in post-transcriptional and translational changes between salt-treated embryo and endosperm. In summary, our results indicate that these regulatory mechanisms, such as alternative splicing, are likely to mediate early responses to salt stress during maize seed germination., (© 2020 John Wiley & Sons Ltd.)

Background: The present study focused on the potential clinical significance of Th-17 cell related inflammatory cytokines in the occurrence and development of neonatal respiratory distress syndrome (NRDS)., Methods: We included 82 NRDS children and 82 healthy controls. NRDS children were divided into the mild and severe group based on the disease severity. The serum samples of the NRDS and non-NRDS children were collected, and the expression levels of IL-17, IL-22, and IL-23 were determined by ELISA method. Moreover, correlation between the levels of the cytokines and the disease severity were analyzed, and receiver operating characteristics curve (ROC) analysis was performed to determine the diagnostic value of the cytokines. Finally, correlation between the lung ultrasound score (LUS) of the NRDS patients and the levels of IL-17 and IL-23 were analyzed., Results: IL-17 and IL-23 were dramatically increased in serum of the NRDS patients compared with the non-NRDS patients; moreover, IL-17 and IL-23 were significantly higher in the severe compared with the mild NRDS group, and the levels of both IL-17 and IL-23 were positively correlated with the disease severity. Furthermore, ROC analysis showed that both IL-17 and IL-23 can distinguish NRDS patient, especially the severe NRDS patients from the non-NRDS patients with high sensitivity and specificity; finally, the levels of IL-17 and IL-23 were positively correlated with the LUS in NRDS patients., Conclusions: IL-17 and IL-23 were up-regulated in NRDS and may serve as sensitive biomarkers for the diagnosis and treatment of the disease.

Objective: To observe the changes of insulin secretion in the early stage of severe scald in rats, and to explore its signal transduction mechanism. Methods: Twenty-four male Wistar rats aged 7 weeks were divided into sham injury alone (SIA) group, sham injury+ BPV (HOpic) (SIB) group, scald alone (SA) group, and scald+ BPV (HOpic) (SB) group using the random number table, with 6 rats in each group. Full-thickness scald of 50% total body surface area was inflicted in rats of SA and SB groups by a 6-s immersion of the abdomen and a 12-s immersion of the back in 94 ℃ hot water. Rats in SIA and SIB groups received sham injuries through immersion of the back and abdomen in 37 ℃ warm water for 6 and 12 seconds respectively. From 0 (immediately) to 2 day (s) after injury, the rats in groups SB and SIB were intraperitoneally injected with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway enhancer BPV (HOpic) solution (0.5 mg/mL) at the dosage of 0.6 mg/kg once a day, and the rats in groups SA and SIA were intraperitoneally injected with the same volume of dimethyl sulfoxide once a day. At post injury hour (PIH) 72, the tail blood of rats was sampled for measuring fasting blood glucose (FBG) with a glucometer, and the pancreatic tissue samples of rats was harvested for observing the pathological manifestations of islets by hematoxylin-eosin staining, counting the docked granules per 10 μm membrane of islet beta cells and calculating the proportion of insulin vesicles through the observation of the ultrastructure of islet beta cells by transmission electron microscope, and detecting the phosphorylation level of Akt in the pancreatic PI3K/Akt signaling pathway by Western blotting. Data were statistically analyzed with one-way analysis of variance and least significant difference test. Results: (1) At PIH 72, the rat FBG levels in SIA and SIB groups were normal and similar ( P >0.05). Compared with the levels of those two groups, the rat FBG level in SA group was increased significantly ( P <0.01), while the level in SB group showed no obvious change ( P >0.05). Compared with that in SA group, the rat FBG level in SB group was decreased significantly ( P <0.01). (2) At PIH 72, the morphology of rat islets was complete and the islet cells distributed regularly in SIA and SIB groups. Compared with those in SIA and SIB groups, the morphology of rat islets was incomplete, the insulin vesicles in islets were common, the islet cells distributed irregularly, and the cytoplasm of some islet beta cells was lightly stained or translucent in SA group; the morphology of islets in SB group did not change obviously. Compared with those in SA group, the morphology of islets was comparatively complete, the insulin vesicles in islets were less common, the islet cells distributed comparatively regularly, and the lightly stained or translucent cytoplasm of islet beta cells was less in SB group. (3) At PIH 72, the number of docked granules per 10 μm membrane of rat islet beta cells and the proportion of insulin vesicles in SIA and SIB groups were similar ( P >0.05). Compared with those in SIA and SIB groups, the number of docked granules per 10 μm membrane of rat islet beta cells in SA group was decreased significantly ( P <0.01), while the proportion of insulin vesicles was increased significantly ( P <0.01); the number of docked granules per 10 μm membrane of rat islet beta cells in SB group was obviously decreased ( P <0.05), while the proportion of insulin vesicles did not change obviously ( P >0.05). Compared with those in SA group, the number of docked granules per 10 μm membrane of rat islet beta cells in SB group was significantly increased ( P <0.01), while the proportion of insulin vesicles was significantly decreased ( P <0.01). (4) At PIH 72, the phosphorylation levels of Akt in SIA, SIB, SA, and SB groups were 0.91±0.03, 0.98±0.03, 0.78±0.08, and 0.87±0.08, respectively. Compared with that in SIA group, the phosphorylation level of Akt was increased obviously in SIB group ( P <0.05) but was decreased significantly in SA group ( P <0.01), while the level in SB group did not change obviously ( P >0.05). Compared with the level in SIB group, the phosphorylation levels of Akt in SA and SB groups were decreased significantly ( P <0.01). Compared with that in SA group, the phosphorylation level of Akt in SB group was increased significantly ( P <0.05). Conclusions: At the early stage post severe scald in rats, the activity of the pancreatic PI3K/Akt signaling pathway and the function of insulin secretion are reduced. Improving the activity of the pancreatic PI3K/Akt signaling pathway in rats can ameliorate the function of insulin secretion and recover the physiological level of blood glucose.

Cold stress profoundly affects plant growth and development and is a key factor affecting the geographic distribution and evolution of plants. Plants have evolved adaptive mechanisms to cope with cold stress. Here, through the genomic analysis of Arabidopsis, three Brassica species and 17 other representative species, we found that both cold-related genes ( CRGs ) and their collinearity were preferentially retained after polyploidization followed by genome instability, while genome-wide gene sets exhibited a variety of other expansion mechanisms. The cold-related regulatory network was increased in Brassicaceae genomes, which were recursively affected by polyploidization. By combining our findings regarding the selective retention of CRGs from this ecological genomics study with the available knowledge of cold-induced chromosome doubling, we hypothesize that cold stress may have contributed to the success of polyploid plants through both increasing polyploidization and selectively maintaining CRGs during evolution. This hypothesis requires further biological and ecological exploration to obtain solid supporting evidence, which will potentially contribute to understanding the generation of polyploids and to the field of ecological genomics., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Foot orthoses (FOs) are commonly used as interventions for individuals with flatfoot. Advances in technologies such as three-dimensional (3D) scanning and 3D printing have facilitated the fabrication of custom FOs. However, few studies have been conducted on the mechanical properties and biomechanical effects of 3D-printed FOs. The purposes of this study were to evaluate the mechanical properties of 3D-printed FOs and determine their biomechanical effects in individuals with flexible flatfoot. During mechanical testing, a total of 18 FO samples with three orientations (0°, 45°, and 90°) were fabricated and tested. The maximum compressive load and stiffness were calculated. During a motion capture experiment, 12 individuals with flatfoot were enrolled, and the 3D-printed FOs were used as interventions. Kinematic and kinetic data were collected during walking by using an optical motion capture system. A one-way analysis of variance was performed to compare the mechanical parameters among the three build orientations. A paired t -test was conducted to compare the biomechanical variables under two conditions: walking in standard shoes (Shoe) and walking in shoes embedded with FOs (Shoe+FO). The results indicated that the 45° build orientation produced the strongest FOs. In addition, the maximum ankle evertor and external rotator moments under the Shoe+FO condition were significantly reduced by 35% and 16%, respectively, but the maximum ankle plantar flexor moments increased by 3%, compared with the Shoe condition. No significant difference in ground reaction force was observed between the two conditions. This study demonstrated that 3D-printed FOs could alter the ankle joint moments during gait., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Kuang-Wei Lin et al.)

Provision of adequate task-oriented training can be difficult for stroke survivors with limited hand movement. The current passive devices are mainly intended for gross grasp and release training. Additional assistive devices are required to improve functional opposition. This paper investigated the functional recovery of chronic stroke patients after using a three-dimensional (3D) printed dynamic hand device (3D-DHD) as an adjunct to conducting a task-oriented approach (TOA). Ten participants were randomly assigned to either the 3D-DHD group (n = 5) or the control group (n = 5). The TOA was used for the 3D-DHD group by using the 3D-DHD twice a week for four weeks, followed by a two-week home program. Only the TOA was used for the control group. The outcome measures, including the box and blocks test (BBT) of manual dexterity and prehensile strength, were conducted at baseline and at follow-up at four and six weeks later. The 3D-DHD group exhibited significantly superior improvements to the control group in the BBT and the palmar pinch force test. Both the groups had significant within-group improvements in the BBT and in all strength measures compared with baseline measurements. The use of 3D-DHD could position stroke-affected hands in coordinated functional opposition and had the potential to facilitate manual dexterity and advanced prehensile movement.

A microRNA (miRNA) is a single-stranded, small and non-coding RNA molecule that contains 20-25 nucleotides. More than 2000 miRNAs have been identified in human genes since the first miRNA was discovered in Caenorhabditis elegans in the early 1990s. miRNAs play a crucial role in various biological processes by regulating gene expression through post-transcriptional mechanisms. The alterations of their levels are associated with various diseases, such as glucometabolic disorder and lipid metabolism disorder. In recent years, miRNAs have been proved to be involved in regulating the functions of pancreatic β-cells, insulin resistance and other biological behaviors related to glucometabolic disorder and the pathogenesis of diabetes mellitus (DM). This review summarized specific miRNAs, including miRNA-375 (miR-375), miRNA-155 (miR-155), miRNA-21 (miR-21), miRNA-33 (miR-33), the let-7 family and some other miRNAs related to glucometabolic regulation, introduced the obstacles and challenges in miRNA therapy, and discussed the prospect of new treatment methods for glucometabolic disorder., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

To investigate the effect of hydrophobic and hydrophilic polypropylene hollow fiber membranes (PPHFMs) applied in membrane bioreactors (MBR), the fouling behaviors of membrane surfaces and pores have been tested. The structural and morphological features on the membrane surface were characterized using attenuated total reflection-Fourier transform infrared spectroscopy, field emission scanning electron microscopy, atomic force microscope, energy dispersive X-ray spectroscopy and laser granularity distribution analysis. The results showed that significantly more polysaccharide, protein and inorganic ingredients were accumulated in the original membrane compared to the hydrophilic membrane. Furthermore, it was found that the pore size influenced the particle distribution and accumulation, such that smaller pore size membranes tended to contain fewer pollutants and a narrow size distribution. Under a constant flux of 11.5 L/m 2  h, the transmembrane pressure (TMP) varied narrowly between 38 and 53 KPa. Alongside this, a relatively hydrophilic membrane (PP-g-AA) showed the characteristics of lower TMP in comparison to hydrophobic membranes (PP). Indeed, the flux recovery was 30% higher than those of the original PPHFM. This investigation broadens our understanding of membrane modifying and fouling behavior in integrated MBRs.

Objective: To investigate the association between Thymidine phosphorylase(TYMP)genetic variation and clinical outcomes of postoperative gastric cancer (GC) patients received capecitabine based regimens. Methods: A total of 198 GC patients underwent surgical treatment and received capecitabine based adjuvant chemotherapy were included in this retrospective study. Peripheral blood and the postoperative tissue specimen of the GC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative GC patients were analysed. Results: Located in the upstream, rs11479 was of clinical significance. The prevalence of rs11479 in TYMP among the GC patients were as follows: CC genotype 125 cases (63.13%), CT genotype 65 cases (32.83%), TT genotype 8 cases (4.04%), minor allele frequency of rs11479 is 0.20. The distribution of three genotypes were in accordance with Hardy-Weinberg Equilibrium ( P =0.901). The analysis results of patients with different genotypes found that the 3-year disease free survival rate of the patients with CT/TT genotype and CC genotype were 73.97% and 65.60%, respectively, which was statistically significant ( P =0.003). In terms of overall survival, the 3-year overall survival rate of the two genotypes were 83.56% and 72.80% ( P =0.012), respectively. Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for disease free survival ( OR =0.55, P =0.011). Safety analysis indicated that there was no significant association between genotypes and grade 2 adverse reaction. Additionally, of the 79 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the wild type CC genotype patients ( P <0.001). Conclusion: The polymorphism rs11479 of TYMP have favorable influence on the clinical outcomes of gastric cancer patients received capecitabine based adjuvant chemotherapy treatment through changing the mRNA expression of TYMP.

The genome of kiwifruit (Actinidia chinensis) was sequenced previously, the first in the Actinidiaceae family. It was shown to have been affected by polyploidization events, the nature of which has been elusive. Here, we performed a reanalysis of the genome and found clear evidence of 2 tetraploidization events, with one occurring ∼50-57 million years ago (Mya) and the other ∼18-20 Mya. Two subgenomes produced by each event have been under balanced fractionation. Moreover, genes were revealed to express in a balanced way between duplicated copies of chromosomes. Besides, lowered evolutionary rates of kiwifruit genes were observed. These findings could be explained by the likely auto-tetraploidization nature of the polyploidization events. Besides, we found that polyploidy contributed to the expansion of key functional genes, e.g., vitamin C biosynthesis genes. The present work also provided an important comparative genomics resource in the Actinidiaceae and related families., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical features diagnostic experience and the surgical management of labyrinthine fistula in chronic suppurative otitismedia. Method: Twenty-four cases(24 ears)of labyrinthine fistula caused by chronic suppurative otitis media that were treated from 2006 to 2013 were reviewed.The fistula test and temporal bone CT scan were performed before the operation, then compare the positive rates between them.In all of these cases, the lesion tissue of fistula is cleaned. Then the fistula was repair of through fascia sealing by temporal myofascial or mastoid periosteum in type Ⅰ and Ⅱ fistula.Semicircular canal occlusion was used in type Ⅲ fistula.Comparison of the effect of fistula typing on preoperative and postoperative hearing. Result: The fistulae were located at the lateral semicircular canal in 23 ears, at the lateral semicircular canal in 1 ears.Temporal bones was positive in 10 cases(41.66％) while fistula test was positive in 9 cases(37.5％). There was no statistically significant difference between the diagnosis of the labyrinthine fistula( P =0.50).The effect of fistula typing on postoperative auditory changes was not statistically significant ( P =0.73). Conclusion: In the preoperative diagnosis of the fistula,the use of fistula test and CT scan simultaneously may increase the accuracy of the diagnostic. However the test results are not reliable when is negative results,intraoperative exploration is the most important method for the diagnosis of labyrinth fistula.Surgery should be based on the type of fistula,size,hearing levels and operation experience., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Angiogenesis serves a role in the growth, metastasis and prognosis of tumors. The aim of the present study was to evaluate the angiogenic ability and clinical significance of the immune biomarker soluble interleukin‑2 receptor (sIL‑2R) in gastric cancer (GC) patients. Serum levels of sIL‑2R were measured in 35 GC patients with different stages of disease and 32 healthy individuals, and it was investigated whether the levels were associated with angiogenesis factors, including vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)‑β1. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without recombinant human (rh)sIL‑2R, VEGF and TGF‑β1 for 24 h, and then the HUVECSs were harvested to determine the degree of angiogenesis. The supernatants were also collected for VEGF and TGF‑β1 testing. Serum levels of sIL‑2R were higher in GC patients than in healthy individuals, as were the levels of VEGF and TGF‑β1. In addition, serum levels of sIL‑2R were positively associated with the levels of VEGF and TGF‑β1. Angiogenesis of HUVECs was also increased by rhsIL‑2R pretreatment. VEGF and TGF‑β1 secretion were also incre-ased in supernatants that were pretreated with rhsIL‑2R. The results of the present study suggested that serum levels of sIL‑2R contributes to the pathophysiology of GC progression and may be used as a prognostic biomarker for GC.

The change in the infrared spectrum of polymer samples with temperature and their differential scanning calorimetry (DSC) experimental results are analyzed. According to the van't Hoff equation at constant pressure, the changes in the absorbance ratio corresponding to high and low vibrational states are calculated, and the apparent enthalpy differences of the vibration energy states transformation of the characteristic group can be obtained. From the experimental results, we can find that characteristic vibration modes of a chemical group in a polymer are under the influence of the glass transition process of the polymer with a different extent. The characteristic vibration modes of the same chemical group behave differently due to the influence of the polymer system at which the chemical moiety is situated.

In the present work, a detailed investigation of Ni(II) hydration in water solutions was carried out using density functional theory (DFT) and extended X-ray absorption fine structure (EXAFS) spectroscopy. The hydrated characteristics of [Ni(H2O)n](2+) clusters, such as energy parameters, atomic charge distributions, and bond parameters, were explored using DFT with Becke's three-parameter exchange potential and the Lee-Yang-Parr correlation functional (B3LYP). DFT calculations indicated that the preferred structure of the first hydration shell of Ni(II) generally has a coordination number of six and is almost unaffected by the water molecules in the outer solvation shell, whereas the structure of the second solvation shell varies as the hydration proceeds. EXAFS measurements are reported for aqueous NiSO4 and Ni(NO3)2 solutions and the Ni(NO3)2·6H2O crystal. Analysis of the EXAFS spectra of these three systems using a multiparameter fitting procedure showed that, in each case, the first coordination shell consists of six water molecules with a Ni-O coordination distance of 2.04 Å, and that there is no Ni-S or Ni-N coordination in the first shell. There was no evidence of outer-shell SO4(2-) or NO3(-) ions substituting inner-sphere water molecules in NiSO4 and Ni(NO3)2. The characteristics of Ni(II) hydration obtained from DFT calculations agreed well with those obtained experimentally using EXAFS.

The purpose of the present study was to develop the Solutol HS15-based doxorubicin submicron emulsion with good stability and overcoming multi-drug resistance. In this study, we prepared doxorubicin submicron emulsion, and examined the stability after autoclaving, the in vitro cytotoxic activity, the intracellular accumulation and apoptpsis of doxorubicin submicron emulsion in MCF-7/ADR cells. The physicochemical properties of doxorubicin submicron emulsion were not significantly affected after autoclaving. The doxorubicin submicron emulsion significantly increased the intracellular accumulation of doxorubicin submicron emulsion and enhanced cytotoxic activity and apoptotic effects of doxorubicin. These results may be correlated to doxorubicin submicron emulsion inhibitory effects on efflux pumps through the progressive release of intracellular free Solutol HS15 from doxorubicin submicron emulsion. Furthermore, these in vitro results suggest that the Solutol HS15-based submicron emulsion may be a potentially useful drug delivery system to circumvent multi-drug resistance of tumor cells.

In the present study, a simple and efficient method for the preparative separation of 3-CQA from the extract of Helianthus tuberosus leaves with macroporous resins was studied. ADS-21 showed much higher adsorption capacity and better adsorption/desorption properties for 3-CQA among the tested resins. The adsorption of 3-CQA on ADS-21 resin at 25°C was fitted best to the Langmuir isotherm model and pseudo-second-order kinetic model. Dynamic adsorption/desorption experiments were carried out in a glass column packed with ADS-21 to optimise the separation process of 3-CQA from H. tuberosus leaves extract. After one treatment with ADS-21, the content of 3-CQA in the product was increased 5.42-fold, from 12.0% to 65.2%, with a recovery yield of 89.4%. The results demonstrated that the method was suitable for large-scale separation and manufacture of 3-CQA from H. tuberosus leaves., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

TP53 and KRAS mutations are commonly found in colorectal tumors. The rates of mutation of these two genes in colorectal carcinoma were compared to better understand their contribution to the disease. Here, colorectal tissue samples were obtained from 49 patients with colorectal adenoma, 90 patients with single primary colorectal carcinoma, 32 patients with multiple primary colorectal carcinoma, and 50 healthy individuals. Real-time PCR was used to amplify exons 5-8 of TP53 and codons 12-13 (exon 1) of KRAS from each sample. Clinical and pathological features of tumor samples were recorded, and these features were compared against mutation status using multivariate logistic regression. The proportions of samples with mutations of KRAS and/or TP53 were significantly different between control individuals and those with colorectal lesions (P < 0.05). Indeed, more than 80% of carcinoma samples were positive for either a KRAS or TP53 mutation. Further, mutations in KRAS and/or TP53 were significantly more common among the two groups with confirmed carcinoma than in individuals with colorectal adenoma (P < 0.05). Interestingly, TP53 mutations were significantly more frequent than KRAS mutations in the colorectal adenoma group (P < 0.01). However, no associations were observed for the frequency of KRAS or TP53 mutations between well-differentiated and poorly-differentiated tumors, different tumor stages, or other clinical and pathological features like age, sex, family history, tumor location, and stage and grade of differentiation. In conclusion, KRAS and TP53 mutations are important contributors to colorectal cancer, and TP53 mutation appears to occur earlier than KRAS mutation.

According to the Stockholm Convention, polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) are classified into unintentionally produced persistent organic pollutants (UP-POPs), and named dioxins. Coke production as a thermal process contains organic matters, metal and chlorine, is considered to be a potential source of dioxins. Intensive studies on the emission of dioxins from coking industry are still very scarce. In order to estimate the emission properties of dioxins through coke production, isotope dilution HRGC/HRMS technique was used to determine the concentration of dioxins through flue gas during heating of coal. Three results were obtained. First, total toxic equivalents at each stationary emission source were in the range of 3.9-30.0 pg x m(-3) (at WHO-TEQ) for dioxins which was lower than other thermal processes such as municipal solid waste incineration. Second, higher chlorinated PCDD/Fs were the dominant congeners. Third, emissions of dioxins were dependent on coking pattern. Stamping coking and higher coking chamber may lead to lower emission.

Although the association between hypoxia-inducible factor-1α (HIF-1α) C1772T polymorphism and risk of malignancy has been widely studied, results from published studies remained controversial. Therefore, the relationship between them was further assessed in this meta-analysis. The databases of PubMed, Embase, and Wanfang were searched, and odds ratio with 95% confidence interval (OR and 95% CI) were used to assess the strength of the association. A total of 38 case-control studies with 23,876 participants were included. Overall, the T allele of HIF-1α C1772T was significantly associated with increased risk of malignancy development (OR and 95% CI 1.18 (1.00-1.38), P = 0.048 for T carriers vs. CC; 1.22 (1.05-1.41), P = 0.010 for T carriers vs. C carriers). When subgroup analyses were conducted, T allele was further found to be associated with increased risk of malignancy development for Asians rather than Caucasians (OR and 95% CI 1.36 (1.10-1.67), P = 0.004 for Asians) and for population-based studies (OR and 95% CI 1.19 (1.01-1.41), P = 0.040). Between-study heterogeneity existed in genetic comparison models, and meta-regression indicated that the participants' ethnicities and types of malignancy might be the sources of heterogeneity. No publication bias was found. In conclusion, this study indicated that HIF-1α C1772T polymorphism was significantly associated with increased risk of malignancy development for Asians. More studies were further required to focus on the relationship between HIF-1α C1772T polymorphism and risk of a specific type of tumor.

Objectives: Unique microRNAs (miRNAs) have been identified in colorectal cancer in recent studies which can be used to accurately diagnose the presence of colorectal cancer and help predict disease recurrence. Differential expression of specific miRNAs in tissues or blood offers the prospect of their use in early detection and screening for colorectal cancer. However, the experiments under different environments would produce different results. The purpose of this study was to get a reliable result on differentially expressed miRNAs related to colorectal cancer by integrating different studies., Materials and Methods: A meta-analysis was performed to review three miRNA microarray datasets from three published literatures that compared the microRNAs expression profiles in colorectal cancer tissues with those in normal colorectal tissues. The R VennDiagram package was applied to identify the overlapping miRNAs with differential expression among these three studies., Results: A total of 175 differentially expressed miRNAs were reported in the three miRNA expression profiling studies that compared colorectal cancer tissues with normal tissues, of which 25 miRNAs were reported at least by two studies including 15 up-regulated miRNAs and 10 down-regulated miRNAs. Among the 25 miRNAs, 15 ones were differentially expressed between early stage colorectal cancer and normal tissues including 11 up-regulated miRNAs and 4 down-regulated miRNAs, of which hsa-miR-195 (down-regulated) and hsa-miR-20a (up-regulated) were shared by these three studies., Conclusions: The 15 differentially expressed miRNAs, especially hsa-miR-195 and hsa-miR-20a may be used as potential biomarkers for early detection and screening of colorectal cancer.

The associations between cyclooxygenase-2 (COX-2) polymorphisms (-765G>C, -1195G>A, and -587G>A) and risk of gastric cancer have been investigated, but the results were inconsistent. The aim of this study was to explore the associations between COX-2 polymorphisms and risk of gastric cancer using a meta-analytic method. We searched the databases of PubMed, Embase, and Wanfang (Chinese database) to identify the eligible studies. Odds ratio and 95 % confidence interval (OR and 95% CI) were used as effect size, and combined analyses were conducted using fixed- or random-effects model. Overall, ten studies for COX-2-765G>C, six studies for -1195G>A, and three studies for -587G>A were included in this study. The results for combined analysis for COX-2-765G>C indicated that C allele was significantly associated with increased risk of gastric cancer compared with G allele, especially for Asians (OR and 95 % CI: 1.58 (1.06-2.35), P(z-test) = 0.03, and P heterogeneity <0.01 for CC+GC vs. GG). In addition, the A allele of COX-2-1195G>A was also significantly associated with risk of gastric cancer compared with G allele (OR and 95 % CI: 1.20 (1.09-1.32), P(z-test) <0.001, and P(heterogeneity) = 0.82 for A carriers vs. G carriers). In contrast, the COX-2-587G>A polymorphism was not associated with risks of gastric cancer. In summary, this meta-analysis indicated that the COX-2-765G>C and -1195G>A polymorphisms were significantly associated with risk of gastric cancer development.

A large contrast in the electrical and thermal conductivities via a first order phase transition in surface-functionalized carbon nanotube(CNT)/hexadecane composites is reported. Surface modification of the CNTs improves the electrical conductivity contrast and the stability of the composites. We demonstrate that, with these composites, the electrical conductivity changes above 10(5) times and the thermal conductivity varies up to 3 times at 18 °C., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Systemic microvascular complications are related to the presence of diabetic neuropathy. This study investigated the associations of blood flow oscillations with peripheral neuropathy in 25 controls and 3 diabetic groups including clinical (24), subclinical (27) and without neuropathy (26). Laser Doppler skin perfusion was transformed into three low-frequency subintervals corresponding to endothelial, neurogenic and myogenic vasomotor controls. The average vasomotion was significantly reduced in clinical neuropathy group and characterized by endothelial and neural but not smooth muscle-related changes. The normalized spectrums revealed a relative increase of myogenic and decrease of neurogenic activity in subclinical neuropathy group. The myogenic component showed a statistically inverse correlation with postural fall in systolic blood pressure (r = -0.32, p < 0.01). The diabetic patients with decreased low-frequency vasomotor responses were associated with increased odds ratio of peripheral neuropathy [odds ratio = 3.51 (95% confidence interval = 1.19-10.31), p = 0.02]. This study elucidated possible interaction between impaired microvascular flow motion and diabetic peripheral neuropathy. The vasomotor changes of skin microcirculation could be detected even in the absence of overt cardiovascular dysfunction.

The field emission performance and structure of the vertically aligned multi-walled carbon nanotube arrays irradiated by energetic C ion with average energy of 40 keV have been investigated. During energetic C ion irradiation, the curves of emission current density versus the applied field of samples shift firstly to low applied fields when the irradiation doses are less than 9.6 x 10(16) cm(-2), and further increase of dose makes the curves reversing to a high applied field, which shows that high dose irradiation in carbon nanotube arrays makes their field emission performance worse. After energetic ion irradiation with a dose of 9.6 x 1016 cm(-2), the turn-on electric field and the threshold electric field of samples decreased from 0.80 and 1.13 V/microm to 0.67 and 0.98 V/microm respectively. Structural analysis of scanning electron microscopy, transmission electron microscopy and Raman spectroscopy indicates that the amorphous carbon nanowire/carbon nanotube hetero nano-structures have been fabricated in the C ion irradiated carbon nanotubes. The enhancement of electron field emission is due to the formation of amorphous carbon nanowires at the tip of carbon nanotube arrays, which is an electron emitting material with low work function.

We studied the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, on colon cancer. The expression of HDACs in colorectal cancer specimens and the effects of SAHA on colon cancer cells and tumors of nude mice were assessed. Treatment with SAHA (3 μm) for 72 h induced downregulation of different subtypes of HDAC proteins and also induced acetylation of histone 3 and histone 4. SAHA significantly inhibited the expression of the oncogenic protein c-myc and also increased the expression of the p53 and Rb proteins. The immunohistochemical staining of HDACs, including HDAC1, HDAC2, HDAC3, and HDAC4, was significantly increased in colorectal adenocarcinoma specimens compared to healthy control tissues. In addition, murine studies showed that 100 mg/kg SAHA administered by intraperitoneal injection significantly induced tumor necrosis and inhibited the growth of colon tumors. Immunohistochemistry of the tumor tissues from nude mice revealed that SAHA inhibited the expression of different subtypes of histone deacetylase, the anti-apoptotic proteins cyclin D1, survivin, and also inhibited cell proliferative as determined by Ki67 expression. SAHA inhibited the growth of colon tumors by decreasing histone deacetylases and the expression of cyclin D1 and survivin in nude mice.

Mesoporous zeolite silicalite-1 and Al-ZSM-5 with intracrystalline mesopores were synthesized with polyelectrolyte-surfactant complex as the template. Complex colloids were first formed by self-assembly of the anionic polymer poly(acrylic acid) (PAA) and the cationic surfactant cetyltrimethylammonium bromide (CTAB) in basic solution. During the synthesis procedure, upon the addition of the silica source, microporous template (tetrapropylammonium hydroxide), and NaCl, these PAA/CTA complex colloids underwent dissociation and gave rise to the formation of hollow silica spheres with mesoporous shells templated by CTAB micelles and PAA domains as the core. Under hydrothermal treatment, the hollow silica spheres gradually merged together to form larger particles with the PAA domains embedded as the space occupant, which acted as a template for intracrystalline mesopores during the crystallization of the zeolite framework. Amphiphilic organosilane was used to enhance the connection between the PAA domain and the silica phase during the synthesis. After calcination, single crystal-like zeolite particles with intracrystalline mesopores of about 5-20 nm were obtained, as characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and N(2) adsorption measurements. With the addition of an aluminum source in the synthesis, mesoporous zeolite Al-ZSM-5 with intracrystalline mesopores was also synthesized, and enhanced catalytic property was observed with mesoporous Al-ZSM-5 in acetalization of cyclohexanone with methanol.

Hydrothermally stable mesoporous aluminosilicates Al-SBA-1 with hierarchical pore structure have been successfully synthesized under alkaline condition at 120 °C by employing organic mesomorphous complexes of polyelectrolyte (poly(acrylic acid) (PAA)) and cationic surfactant (hexadecyl pyridinium chloride (CPC)) as template. The Si/Al ratio could be as high as 5 and the incorporation of Al into the silica framework did not disturb the well-ordered cubic Pm ̅3n mesostructure. Meanwhile, the incorporation of Al could greatly increase the specific surface area and pore volume of the samples. The Al-SBA-1 materials exhibited a high hydrothermal stability and remained stable even after being treated in boiling water for 10 days. The catalytic activity of the Al-SBA-1 materials was investigated by employing the Friedel-Crafts alkylation of toluene with benzyl alcohol as a model reaction and they exhibited excellent catalytic property due to the incorporated acid sites and the hierarchically mesoporous structure., (This journal is © The Royal Society of Chemistry 2012)