Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage.

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

[Labor progression characteristics of primiparous term singleton pregnant women complicated with adenomyosis].

Objective: To analyze the labor progression characteristics of primiparous term singleton pregnant women with adenomyosis. Methods: From April 2014 to May 2021, pregnant women underwent regular antenatal examination in Peking University Third Hospital were enrolled in this retrospective study, 109 primiparous term pregnant women with adenomyosis who underwent singleton, primipara, cephalic and vaginal delivery were referred as the adenomyosis group, while 109 pregnant women without adenomyosis primiparous term pregnant women at the same time were referred as the control group. The general clinical information, labor process intervention, pregnancy outcomes and labor course time of the two groups were analyzed. Results: (1) General clinical conditions: the pre-pregnancy uterine volume of the adenomyosis group was larger than that of the control group [(66.8±23.7) vs (41.4±13.1) cm3, P<0.05]. The proportion of assisted reproductive pregnancy and endometriosis in the adenomyosis group were higher than those in the control group [31.2% (34/109) vs 7.3% (8/109); 31.2% (34/109) vs 5.5% (6/109); all P<0.05]. There were no significant differences in maternal age, gestational age at delivery, pre-pregnancy body mass index, gestational weight gain, gravidity, incidence of pregnancy complications (gestational diabetes mellitus, pre-eclampsia and thyroid diseases) and premature rupture of membranes between the two groups (all P>0.05). (2) Labor process intervention and maternal and fetal outcomes: postpartum hemorrhage was higher in the adenomyosis group than the control group (median: 300 vs 260 ml, P=0.018). There were no significant differences in the proportion of labor onset, use of oxytocin, artificial rupture of membranes, perineal laceration Ⅲ and above, episiotomy, newborn weight and 1-minute Apgar score between the two groups (all P>0.05). (3) Time of labor process: there were no significant differences between the two groups in the time required for the first stage, third stage, total stage and cervical dilation 0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7 cm (all P>0.05). The time required for cervical dilation 7-8, 8-9, 9-10 cm and the second stage of labor in adenomyosis group (median: 20, 18, 15 and 12 minutes, respectively) were shorter than those of the control group (median: 23, 23, 23 and 26 minutes, respectively), and the differences were statistically significant (all P<0.05). (4) The effect of endometriosis on labor: there was no significant difference in the effect of endometriosis on labor in adenomyosis group (P>0.05). Conclusions: The labor process of primiparous term pregnant women with adenomyosis is significantly accelerated after the cervical dilatation for 7 cm, which should be closely observed. The third stage of labor course is managed aggressively with drugs to prevent postpartum hemorrhage.

Site-directed mutation of ß-galactosidase from Streptococcus thermophilus for galactooligosaccharide-enriched yogurt making.

ß-Galactosidase is one of the most important enzymes used in dairy processing. It converts lactose into glucose and galactose, and also catalyzes galactose to form galactooligosaccharides (GOS), so-called prebiotics. However, most of the ß-galactosidases from the starter cultures have low transgalactosylation activities, the process that results in galactose accumulation in yogurt. Here, a site-directed mutation strategy was attempted, to genetically modify ß-galactosidase from Streptococcus thermophilus. Out of 28 Strep. thermophilus strains, a ß-galactosidase gene named bgaQ, encoded for high ß-galactosidase hydrolysis activity (BgaQ), was cloned from the strain Strep. thermophilus SDMCC050237. It was 3,081 bp in size, with 1,027 deduced amino acid residuals, which belonged to the GH2 family. After replacing the Tyr801 and Pro802 around the active sites of BgaQ with His801 and Gly802, the GOS synthesis of the generated mutant protein BgaQ-8012 increased from 20.5% to 26.7% at 5% lactose, and no hydrolysis activity altered obviously. Subsequently, the purified BgaQ or BgaQ-8012 was added to sterilized milk inoculated with 2 starters from Strep. thermophilus SDMCC050237 and Lactobacillus delbrueckii ssp. bulgaricus ATCC11842. The GOS yields with added BgaQ or BgaQ-8012 increased to 5.8 and 8.3 g/L, respectively, compared with a yield of 3.7 g/L without enzymes added. Meanwhile, the addition of the BgaQ or BgaQ-8012 reduced the lactose content by 49.3% and 54.4% in the fermented yogurt and shortened the curd time. Therefore, this study provided a site-directed mutation strategy for improvement of the transgalactosylation activity of ß-galactosidase from Strep. thermophilus for GOS-enriched yogurt making.

[Analysis of invalid patents associated with schistosomiasis control filed by Chinese applicants].

The invalid patents associated with schistosomiasis control were retrieved in the Chinese Patent Database of China National Intellectual Property Administration, the Baiten database and the incoPat database, and the overall trends, legal status, types, patent indexing and technical fields of all retrieved invalid patents were analyzed. As of December 30, 2020, there were totally 859 patents relating to schistosomiasis control, and 512 were invalid patents, with an invalid rate of 59.6%. The number of patent applications and invalid patents peaked in 2018, including 71 patent applications and 53 invalid patents. Among the 511 schistosomiasis control-related invalid patents with complete records, there were 425 invention patents, 81 utility model patents and 5 design patents, and 219 patents (42.9%) were invalid due to the termination of the patented right and 292 (57.1%) due to loss of the right for patent applications. The major technical points included medicines (chemicals), basic research, devices and detections, and the specialized fields were mainly concentrated in A61P33, G01N33, C12N15, C07K14 and A01N65. Our data demonstrate a high invalid rate of patents relating to schistosomiasis control in China. Secondary development and mining of the invalid patents in relation to schistosomiasis are recommended to make use of their values in the national schistosomiasis elimination program of China.

Nonequilibrium pattern formation in circularly confined two-dimensional systems with competing interactions.

We numerically investigate the nonequilibrium behaviors of classic particles with competing interactions confined in a two-dimensional logarithmic trap. We reveal a quench-induced surprising dynamics exhibiting rich dynamic patterns depending upon confinement strength and trap size, which is attributed to the time-dependent competition between interparticle repulsions and attractions under a circular confinement. Moreover, in the collectively diffusive motions of the particles, we find that the emergence of dynamic structure transformation coincides with a diffusive mode transition from superdiffusion to subdiffusion. These findings are likely useful in understanding the pattern selection and evolution in various chemical and biological systems in addition to modulated systems, and add a new route to tailoring the morphology of pattern-forming systems.

Structural transitions for 2D systems with competing interactions in logarithmic traps.

We propose a confinement model and study numerically the structural properties of particles with competing interactions in logarithmic traps (i.e., the confinement potential is a logarithmic function). A rich variety of cluster structures are observed as a function of trap steepness, trap size, and particle density. In addition to the consistent results with previous studies for a harmonic confinement, we observe some new stable structures, including a hybrid cluster structure consisting of clumps surrounded by a circular stripe, parallel stripes, or homogeneous voids surrounded by a ringlike arrangement of clumps, and a gear-like cluster with fringed outer rims evenly arranged along the circumference. Our work reveals that such self-organized structures arise due to the radial density reconfiguration in a finite confined system corresponding to the unconstrained systems, which is controlled by the interplay between the long-range repulsions and the attractions to the minimum of the confinement potential. Such results are likely relevant in understanding the structural properties of confined mermaid systems.

Parasitological and molecular detection of human fascioliasis in a young man from Guizhou, China.

A 24-year-old man born in Guizhou province was diagnosed with obstructive jaundice and bile duct stones in 2013. Four living trematodes were found during laparotomy and cholecystectomy. Based on the morphology and molecular genetics analysis of internal transcribed spacer and pcox1 genes of the flatworm specimens, the trematodes from the patient were confirmed to be Fasciola hepatica. This report provided the clinical and molecular diagnosis information on human fascioliasis, which is an emerging sanitary problem still ignored in China. Human fascioliasis constantly occurs due to climatic changes and frequency of human travel. Therefore, it deserves more attention from physicians working in both developing and developed countries.

Parasitological and molecular detection of human fascioliasis in a young man from Guizhou, China

@#A 24-year-old man born in Guizhou province was diagnosed with obstructive jaundice and bile duct stones in 2013. Four living trematodes were found during laparotomy and cholecystectomy. Based on the morphology and molecular genetics analysis of internal transcribed spacer and pcox1 genes of the flatworm specimens, the trematodes from the patient were confirmed to be Fasciola hepatica. This report provided the clinical and molecular diagnosis information on human fascioliasis, which is an emerging sanitary problem still ignored in China. Human fascioliasis constantly occurs due to climatic changes and frequency of human travel. Therefore, it deserves more attention from physicians working in both developing and developed countries.

A feasible strategy to balance the crystallinity and specific surface area of metal oxide nanocrystals.

Practical, efficient synthesis of metal oxide nanocrystals with good crystallinity and high specific surface area by a modified polymer-network gel method is demonstrated, taking ZnO nanocrystals as an example. A novel stepwise heat treatment yields significant improvement in crystal quality. Such nanophase materials can effectively degrade common organic dyes under solar radiation and can perform very well in photo-assisted detection of NO2 gas. Other typical metal oxide nanocrystals with good crystallinity and high specific surface area were also synthesized successfully under similar conditions. This work provides a general strategy for the synthesis of metal oxide nanocrystals, balancing the crystallinity and specific surface area.

[Clinical analysis of cervical posterior internal fixation titanium plate and silk suspension internal fixation cervical spondylosis].

Objective: To evaluate the clinical effect and imaging evaluation of cervical spine myelopathy treated with Centerpiece. Methods: A retrospective study of 60 patients underwent posterior cervical spine surgery because of cervical myelopathy in Spinal Department of Peking University People's Hospital from July 2011 to January 2013.According to the different fixation methods, all patients were divided into cervical posterior open-door Centerpiece fixation group (group A) and cervical posterior open-door silk suspension fixation group (group B). There were 40 patients in group A, including 25 males and 15 females, mean age (59.7±11.9) years old, average course of disease before surgery (53.6±61.5) months, average follow-up time (28.5±3.1) months after operation.There were 20 patients in group B, including 15 males and 5 females, mean age (58.3±9.6) years old, average course of disease before surgery (50.4±14.9) months, average follow-up time (28.3±1.9) months after operation.The operation time, intraoperative blood loss, postoperative drainage, preoperative and postoperative Japanese Orthopaedic Association(JOA) score, the neck disability index(NDI) score, visual analog scale (VAS) score, postoperative axial pain, C(5) nerve root palsy, postoperative "re-closing" and other related complications were observed.Imaging assessment projects include: before and after surgery of cervical curvature, range of motion(ROM), spinal anteroposterior diameter, spinal canal expansion rate, the whole spinal cord backward shift distance and area of the spinal canal and the opening angle. Results: There was no significant difference in general data between the two groups (P>0.05). Group A the average operation time was(117.7±23.4)min, the average amount of operative bleeding was (152.0±122.7) ml, and the postoperative drainage volume was (268.7±222.1) ml.The average operation time of group B was (141.7±23.9) min, the average amount of operative bleeding was (166.7±42.5) ml, and the postoperative drainage volume of group B was (255.3±47.0) ml.There was no significant difference between the two groups in the amount of operative bleeding and postoperative drainage volume (both P>0.05), the operation time between the two groups was statistically significant (P<0.05). At the end of the follow-up, the JOA score, NDI score, and VAS score were significantly improved (P<0.05) in both group A and group B and there was no significant difference between the two groups (P>0.05). C(5) nerve root paralysis was not occurred in both two groups after operation.There were 1 case of axial pain in the group A and 7 cases in the group B and there were significant differences between the two groups (P<0.05). The group A was not found "re-closing" during the follow-up and 12 patients of group B found to be "re-closing" phenomenon, there were statistically different between the two groups (P<0.05). Comparison of preoperative and postoperative, there were no significant differences in cervical curvature and ROM in both groups (P>0.05). Butthe spinal canal diameter and the vertebral canal area were statistically different after surgery (P<0.05). There was no statistical difference between the two groups of cervical curvature and ROM (P>0.05). There was no statistical difference between the two groups of spinal canal diameter, spinal canal area and spinal canal diameter enlargement rate(P>0.05). There was no statistical difference between the two groups of the whole spinal cord backward shift distance(P>0.05). There were significant differences between the two groups at the angle of the open door (P<0.05). Conclusion: Centerpiece cervical posterior titanium plate can achieve good clinical efficacy in the treatment of multi segmental spinal cervical spondylosis.

Production of Enzymes from Marine Actinobacteria.

Marine actinobacteria are well recognized for their capabilities to produce valuable natural products, which have great potential for applications in medical, agricultural, and fine chemical industries. In addition to producing unique enzymes responsible for biosynthesis of natural products, many marine actinobacteria also produce hydrolytic enzymes which are able to degrade various biopolymers, such as cellulose, xylan, and chitin. These enzymes are important to produce biofuels and biochemicals of interest from renewable biomass. In this chapter, the recent reports of novel enzymes produced by marine actinobacteria are reviewed, and advanced technologies that can be applied to search for novel marine enzymes as well as for improved enzyme production by marine actinobacteria are summarized, which include ribosome engineering, genome mining, as well as synthetic biology studies.

Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways.

Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. The present study investigated the effects of DHA on the lipid peroxidation, the level of inflammatory cytokines and neuron apoptosis in the hippocampal neurons in high-glucose condition. High-glucose administration increased the level of tumor necrosis factor α (TNF-α) and IL-6, induced oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia.

Human leucocyte antigen-Bw4 and Gag-specific T cell responses are associated with slow disease progression in HIV-1B-infected anti-retroviral therapy-naive Chinese.

In China, the majority of human immunodeficiency virus (HIV) infections are predominately subtype B. It is important to characterize the HIV-1 subtype B-specific and its T cell response within the Chinese population, with the aim of identifying protective correlates of immunity to control HIV-1 infections. In this study, we performed a comprehensive analysis looking into the magnitude/strength of T cell responses directed at the Gag protein of the HIV-1 subtype B, one of the most conserved HIV-1 proteins. The study group consisted of anti-retroviral native and chronic HIV-1 subtype B-infected individuals. We used enzyme-linked immunospot (ELISPOT) assay to quantify the total T cell responses to HIV-1 Gag at the single peptide level. Twenty-eight (38%) peptides were recognized in 24 (82·8%) individuals. The p24 was identified as the most frequently recognized subunit protein with the greatest T cell response in the test, which correlated positively with CD4(+) T cell count and inversely with viral load (VL). At the level of the human leucocyte antigen (HLA) supertypes, we detected the highest levels and a significant correlation with both the CD4(+) T cell count and the VL with Gag T cell responses in Bw4/Bw4. These findings demonstrate that (i) the HIV-1B Gag p24-specific immune responses play an important role in controlling viral replication and slowing clinical progression; and (ii) HLA-Bw4/Bw4 allele has stronger T cell responses, which is associated with slow clinical progression in Chinese HIV patients.

Dietary ω-3 polyunsaturated fatty acids improves learning performance of diabetic rats by regulating the neuron excitability.

Previous research has demonstrated that diabetes induced learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids (PUFA), have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. Sprague-Dawley rats were used in the present study to investigate the effect of fish oil supplementation on spatial learning and memory of streptozotocin (STZ)-induced diabetic rats with the Morris Water Maze. The excitability of CA1 pyramidal neurons and the related ionic currents was also examined. Diabetes impaired spatial learning and memory of rats. Diabetes decreased the sodium currents and increased the potassium currents, and further led to the reduction of excitability of CA1 pyramidal neurons, effects which may contribute to the behavioral deficits. Fish oil dietary supplementation decreased the transient currents and Kv4.2 expression in the hippocampus and partially improved learning performance of diabetic rats. The results of the present study suggested that sodium and potassium currents contributed to the inhibitory effect of diabetes on neuron excitability, further influencing learning and memory processing. Dietary fish oil may modulate the membrane excitability and is a possible strategy for preventing the impairments of diabetes on hippocampal function.

Sleep deprivation impairs spatial learning and modifies the hippocampal theta rhythm in rats.

Previous work from our laboratory suggests that paradoxical sleep deprivation (PSD) decreases persistent sodium currents and hyperpolarization-activated cation currents in CA1 pyramidal neurons, and this leads to decreases in neuron excitability. Here, we further investigate the mechanisms of rhythmic theta-range activity in the hippocampus by examining the resonance characteristics of hippocampal pyramidal neurons. Sleep deprivation (SD) interfered with the rhythmic activity of theta band in the hippocampus, which may be involved in the deficit of the spatial learning ability of rats. Additionally, SD changes the voltage dependence of resonance. The effect of SD on the ion currents may contribute to the alternation of the theta resonance of neurons and further influence the physiological function. These results suggest that changes in neuron resonance lead to changes in the generation of rhythmic theta activity, and may contribute to behavioral deficits associated with theta activity during learning and memory tasks. We suggest the resonant properties of hippocampal neurons are potential targets for preventing deleterious effects of sleep deprivation.

Depletion of CD4+CD25+ regulatory T cells enhances natural killer T cell-mediated anti-tumour immunity in a murine mammary breast cancer model.

Both invariant natural killer T (NK T) cells and CD4(+)CD25(+) T regulatory cells (T(regs)) regulate the immune system to maintain homeostasis. In a tumour setting, NK T cells activated by alpha-galactosylceramide (alpha-GalCer) execute anti-tumour activity by secreting cytokines. By contrast, T(regs) intrinsically suppress antigen-specific immune responses and are often found to be elevated in tumour patients. In this study, we have shown that T(regs) regulate NK T cell function negatively in vitro, suggesting a direct interaction between these cell types. In a murine mammary tumour model, we demonstrated that administration of either alpha-GalCer or anti-CD25 antibody alone markedly suppressed tumour formation and pulmonary metastasis, and resulted in an increase in the survival rate up to 44% (from a baseline of 0%). When treatments were combined, depletion of T(regs) boosted the anti-tumour effect of alpha-GalCer, and the survival rate jumped to 85%. Our results imply a potential application of combining T(reg) cell depletion with alpha-GalCer to stimulate NK T cells for cancer therapy.

Peak effect in the critical current of type II superconductors with strong magnetic vortex pinning.

We perform 2D Langevin simulations studying the peak effect (PE) of the critical current taking into account the temperature dependence of the competing forces. We observe and report that the PE results from the competition of vortex-vortex interactions and vortex-pin interactions which have different temperature dependencies. The simulations reveal that the PE can take place only for certain pinning strengths, densities of pinning centers, and driving forces, which is in good agreement with experiments. No apparent vortex order-disorder transition is observed across the PE regime. In addition, the PE is a dynamical phenomenon, and thermal fluctuations can speed up the process for the formation of the PE.

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa.

For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in a prime-boost regimen by a DNA plasmid and modified vaccinia virus Ankara (MVA). Here, we describe engineering and preclinical development of a second immunogen RENTA, which will be used in combination with the present vaccine in a four-component DNA/HIVA-RENTA prime-MVA/HIVA-RENTA boost formulation. RENTA is a fusion protein derived from consensus HIV clade A sequences of Tat, reverse transcriptase, Nef and gp41. We inactivated the natural biological activities of the HIV components and confirmed immunogenicities of the pTHr.RENTA and MVA.RENTA vaccines in mice. Furthermore, we demonstrated in mice and rhesus monkeys broadening of HIVA-elicited T-cell responses by a parallel induction of HIVA- and RENTA-specific responses recognizing multiple HIV epitopes.

Identification of the immunodominant regions of the Em18 antigen and improved serodiagnostic specificity for alveolar echinococcosis.

The aim of this work was to identify the immunodominant regions of the Em18 antigen to improve the specificity in diagnosis of alveolar echinococcosis (AE). Two recombinant antigens ReEm18-1 and ReEm18-2, which have the same sequence except that nine amino acid residues are absent in ReEm18-2, were tested by ELISA and Western Blot (WB) for their diagnostic efficiency. Serological evaluation of the two antigens demonstrated that the sensitivity of both antigens was 95.5% in ELISA and WB, and the specificity was 93.6% and 95.7% in ELISA, and 81.4% and 82.9% in WB, respectively. Five more expression clones (EmS1-EmS5), which contain different regions of the Em18 sequence, were constructed for defining the immunodominant regions of the antigen. Fourteen monoclonal antibodies (mAbs) against ReEm18-2 antigen and the sera from different groups of patients were used to identify the epitope regions of the five antigen fragments. Results showed that the epitopes recognized by the mAbs are located in the N-terminal third of the sequence, but the immunodominant area recognized by native serum antibodies may be located further downstream (C-terminal) in the sequence. The nonspecific cross-reactivity is due to epitopes present in the C-terminal third of the sequence. The antigen fragments that contain the first two-thirds of the sequence have the same sensitivity to AE sera as those of the ReEm18-1 and ReEm18-2 antigens, but removal of the C-terminal third of the sequence improved the specificity of the assay from 93.6% to 99.3% (ELISA) and 81.4% to 90.7% (WB). We conclude that the necessary part of the ReEm18 antigen sequence for AE diagnosis is the N-terminal half to two-thirds of the entire sequence.