Cystic angiomatosis in children: clinical experience and review of literature.

BACKGROUND: Cystic angiomatosis is a rare benign disease manifesting as multiple lytic and sclerotic bone lesions, described as the proliferation of vascular and lymphatic channels lined by a single layer of endothelial cells. However, the potential pathogenetic mechanism of the disease still remains unknown. Here, we reported a case of cystic angiomatosis with multifocal bone lesion evaluated by whole exome sequencing. CASE DESCRIPTION: In this presentation, we reported a case of an 11-year-old boy with pain in his chest. Computed tomography (CT) revealed the multiple lytic of the bone in the ribs, clavicle, vertebra thoracalis, skull, mandibula, shoulder blade, etc. The blood test showed ALP to be 393U/L and VEGF to be 287.26 pg/ml. The patient was performed with an open biopsy in the ribs and was diagnosed with cystic angiomatosis. Besides, the whole exome sequencing reported the single-nucleotide substitutions in the coding region of BRIP1, CHEK2, GRM4, and MUC16. Then, the upregulated genes involved CASC15, CENPF, ABCA13, ALK, BLM, and FGFR3. CONCLUSIONS: In this article, we report a rare case of cystic angiomatosis in a child with abnormal VEGF and ALP reported by peripheral blood examination. The whole exome sequencing could provide the reference for the potential molecular mechanism in the diagnosis and treatment of cystic angiomatosis.

The comparison of the wisdom view in Chinese and Western cultures.

Wisdom views in different cultural contexts are closely connected with the corresponding culture's worldview. Some results are found by comparing the wisdom concepts in Chinese and Western cultures: Firstly, the early wisdom concepts, both in China and the West, contain the elements of intelligence and virtue. Whereas, from the Enlightenment to the Piagetian school, the western concept of wisdom has then shifted to the role of cognition and knowledge; By contrast, the traditional Chinese wisdom concept has been treating wisdom as a virtue. Modern Chinese and western wisdom psychologists are inclined to accept the wisdom meta-theory of "integration of intelligence and virtue". Secondly, both Chinese and the Western philosophy advocate using wisdom to solve real-life problems. Western thinkers focus on practical problems in the material world, i.e. reconciling conflicts between people and the world through understanding and changing the environment. However, Chinese philosophers focus on internal spiritual problems, i.e. improving the individual realm to solve the contradictions inside oneself. Thirdly, both China and the West highlight the comprehensive application of multiple thinking modes. While comparing with the west, which is excelled in using logical and analytical thinking modes and utilizing rational cognition, China is far better at using dialectical and holistic thinking modes and applying intuitive comprehension.

Embryos aggregation improves development and imprinting gene expression in mouse parthenogenesis.

Mouse parthenogenetic embryonic stem cells (PgESCs) could be applied to study imprinting genes and are used in cell therapy. Our previous study found that stem cells established by aggregation of two parthenogenetic embryos at 8-cell stage (named as a2 PgESCs) had a higher efficiency than that of PgESCs, and the paternal expressed imprinting genes were observably upregulated. Therefore, we propose that increasing the number of parthenogenetic embryos in aggregation may improve the development of parthenogenetic mouse and imprinting gene expression of PgESCs. To verify this hypothesis, we aggregated four embryos together at the 4-cell stage and cultured to the blastocyst stage (named as 4aPgB). qPCR detection showed that the expression of imprinting genes Igf2, Mest, Snrpn, Igf2r, H19, Gtl2 in 4aPgB were more similar to that of fertilized blastocyst (named as fB) compared to 2aPgB (derived from two 4-cell stage parthenogenetic embryos aggregation) or PgB (single parthenogenetic blastocyst). Post-implantation development of 4aPgB extended to 11 days of gestation. The establishment efficiency of GFP-a4 PgESCs which derived from GFP-4aPgB is 62.5%. Moreover, expression of imprinting genes Igf2, Mest, Snrpn, notably downregulated and approached the level of that in fertilized embryonic stem cells (fESCs). In addition, we acquired a 13.5-day fetus totally derived from GFP-a4 PgESCs with germline contribution by 8-cell under zona pellucida (ZP) injection. In conclusion, four embryos aggregation improves parthenogenetic development, and compensates imprinting genes expression in PgESCs. It implied that a4 PgESCs could serve as a better scientific model applied in translational medicine and imprinting gene study.

Traumatic irreducible dislocation of the fifth metatarsophalangeal joint in pediatrics: case report and clinical experience.

Dislocation of the metatarsophalangeal joint (MTPJ) by trauma commonly occurs in adults. Most dislocations of the MTPJ could be reduced by closed reduction. However, isolated traumatic irreducible dislocation of the fifth MTPJ is an extremely rare injury, particularly in children. We report the case of a 10-year-old boy with irreducible dislocation of the fifth MTPJ who presented with a dorsiflexion injury of the right foot 1 year previously. Closed reduction was attempted but failed. Computed tomography showed the dorsolateral dislocation of the fifth MTPJ. We performed an open reduction and metatarsal bone osteotomy, with a short osteotomy at approximately 0.8 cm. The osteotomy was adjusted to a reduction of the MTPJ and fixation by a lock compression plate. The distal growth plate in the metatarsal bone was protected to avoid pre-closure of the growth plate. There were no instances of dislocation or signs of avascular necrosis of the head of the metatarsal bone. The results of this study demonstrated that open reduction and metatarsal bone osteotomy could be an optional treatment for irreducible dislocation of the fifth MTPJ in children. We should pay more attention to the distal growth plate in the metatarsal bone to avoid pre-closure of the growth plate.

Implications of carbon catabolite repression for Aspergillus-based cell factories: A review.

Carbon catabolite repression (CCR) is a global regulatory mechanism that allows organisms to preferentially utilize a preferred carbon source (usually glucose) by suppressing the expression of genes associated with the utilization of nonpreferred carbon sources. Aspergillus is a large genus of filamentous fungi, some species of which have been used as microbial cell factories for the production of organic acids, industrial enzymes, pharmaceuticals, and other fermented products due to their safety, substrate convenience, and well-established post-translational modifications. Many recent studies have verified that CCR-related genetic alterations can boost the yield of various carbohydrate-active enzymes (CAZymes), even under CCR conditions. Based on these findings, we emphasize that appropriate regulation of the CCR pathway, especially the expression of the key transcription factor CreA gene, has great potential for further expanding the application of Aspergillus cell factories to develop strains for industrial CAZymes production. Further, the genetically modified CCR strains (chassis hosts) can also be used for the production of other useful natural products and recombinant proteins, among others. We here review the regulatory mechanisms of CCR in Aspergillus and its direct application in enzyme production, as well as its potential application in organic acid and pharmaceutical production to illustrate the effects of CCR on Aspergillus cell factories.

rRNA genes are not fully activated in mouse somatic cell nuclear transfer embryos.

The well known and most important function of nucleoli is ribosome biogenesis. However, the nucleolus showed delayed development and malfunction in somatic cell nuclear transfer (NT) embryos. Previous studies indicated that nearly half rRNA genes (rDNA) in somatic cells were inactive and not transcribed. We compared the rDNA methylation level, active nucleolar organizer region (NORs) numbers, nucleolar proteins (upstream binding factor (UBF), nucleophosmin (B23)) distribution, and nucleolar-related gene expression in three different donor cells and NT embryos. The results showed embryonic stem cells (ESCs) had the most active NORs and lowest rDNA methylation level (7.66 and 6.76%), whereas mouse embryonic fibroblasts (MEFs) were the opposite (4.70 and 22.57%). After the donor cells were injected into enucleated MII oocytes, cumulus cells and MEFs nuclei lost B23 and UBF signals in 20 min, whereas in ESC-NT embryos, B23 and UBF signals could still be detected at 60 min post-NT. The embryos derived from ESCs, cumulus cells, and MEFs showed the same trend in active NORs numbers (7.19 versus 6.68 versus 5.77, p < 0.05) and rDNA methylation levels (6.36 versus 9.67% versus 15.52%) at the 4-cell stage as that in donor cells. However, the MEF-NT embryos displayed low rRNA synthesis/processing potential at morula stage and had an obvious decrease in blastocyst developmental rate. The results presented clear evidences that the rDNA reprogramming efficiency in NT embryos was determined by the rDNA activity in donor cells from which they derived.

Association between the interleukin-4, interleukin-13 polymorphisms and asthma: a meta-analysis.

A numbers studies had been reported that the polymorphisms in the Interleukin 4 (IL-4) and Interleukin 13 (IL-13) genes were associated with susceptibility to asthma. However, the results were inconsistent and inconclusive. We carried out a meta-analysis of case-control genetic association studies to assess whether the combined data showed this association by using a genetic model-free approach. Thirty studies (total 12,781 asthma and 11,500 controls) for the IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A with asthma were included in the meta-analysis. The results indicated that there were an association between the IL-4 C-33T (P = 0.006) and C-589T (P = 0.04), IL-13 C-1112T (P = 0.002) and G+2044A (P = 0.04) and susceptibility to asthma. And the definition of asthma subgroup meta-analysis demonstrates that the IL-4 C-33T is not associated with nonatopic or atopic, and IL-4 C-589T and IL-13 C-1112T polymorphisms are not associated with atopic. In the ethnicity subgroup meta-analysis, the IL-4 -589T (P = 0.003) and the IL-13 -1112T (P < 0.00001) alleles are associated with asthma among Caucasian, but not on the IL-13 +2044A allele. In conclusion, IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A could be proposed as asthma susceptible SNPs. Further investigation in larger studies and meta-analysis is required.

[The infection status of Leptospira in rodents on the Heixiazi island of Heilongjiang province, China,in 2011].

OBJECTIVE: To study the infection status of Leptospira in rodents on Heixiazi island Heilongjiang province in 2011. METHODS: A total of 356 rodents were captured by night trap on the Heixiazi island from April to October 2011. The kidney tissue samples were collected by asepsis operation and the genomic DNA were extracted from them. Leptospira strains were confirmed by polymerase chain reaction(PCR) amplification of the 482 bp 23 S rDNA gene. Fifteen PCR products selected by the month were purified and sequenced by the methods of Sanger dideoxy, the sequences then compared with other Leptospira strains in Genebank, and phylogenetic analyses were drafted by software Mega 4.0. RESULTS: Among 356 rodents, the dominant species were Clethrionomys rutilus (39.3%, 140/356) and Apodemus agrarius (36.0%, 128/356). The infection rate of Leptospira was 11.0%, with 39 rodent samples detected positive. All the rodent species were infected except for Rattus norvegicus. The infection rate was 9.4% (12/128) in Apodemus agrarius, 12.9%(18/140) in Clethrionomys rutilus, 10.8%(7/65) in Microtus fortis Buchner. No significant difference was found between the infection rate and the species of rodents by chi square test(χ(2) = 1.92, P > 0.05). Among months, the infection rate was 5.6% (4/72) in May, 8.8% (5/57) in June, 12.8% (5/39) in July, 9.8% (5/51) in August, 33.3% (11/33) in September, 22.5% (9/40) in October,but no infection in April. There was significant difference in infection in different months (χ(2) = 32.92, P < 0.05). All the Leptospira in rodents on the Heixiazi island were in the same phylogenetic branch with a high similarity of 97.1%-99.6%, close with the Australia strain U90865 by the similarity above 96.3%. CONCLUSION: Leptospira is probably prevalent in rodents on the Heixiazi island, and the phylogene of the strains were similar. The infection rate in rodents was significantly different in months but not in hosts.

[Dynamic accumulation of three main triterpenic acids in submerged cultivation mycelium of Poria cocos].

OBJECTIVE: To study the dymamic accumulation of triterpenic acids production in submerged cultivation mycelium of Poria cocos. METHOD: Liquid culture method of P. cocos was established and RP-HPLC was applied to determine the contents of three main triterpenic acids dehydrotumulosic acid (DTA), 3-epi-dehydrotumulosic acid (eDTA) and polyporenic acid C (PAC) in submerged cultivation mycelium P. cocos at different culture stages and the contents were compared with cultivated P. cocos. The HPLC method is as follows, column: Plastisil ODS (4.6 mm x 250 mm, 5 microm); mobile phase: ACN/0.5% phosphate (80:20); flow rate: 1.0 mL . min-1; detective wavelength: 242 nm. RESULT: The maximum biomass occurred at the 8th d after inoluctation, however, the contents and yield of three compounds increased till the 17th day. The contents of three compounds were 1. 2% (DTA), 0. 42% (eDTA) and 1.0% (PAC) at the 17th day after inoculation, which were significantly higher than that in cultivated material [0.2% (DTA), 0. 12(eDTA) and 0. 16% (PAC) ]. Furthermore, a correlation analysis between the content ratios of three independent compounds was carried out. The results showed that DTA negatively correlated with eDTA and PAC, with R2 of 0. 857 6 and 0. 971 7, respectively, which suggested the role of DTA as an important intermediate in the biosynthesis of triterpenic acids in P. cocos. CONCLUSION: The sum content of three main terpenoids in submerged cultivation mycelium P. cocos was 5. 55 times as that in cultivated material, which strongly suggested the possibility of fermentation in the production of medicinally important triterpenic acids in the future.

A Review on the Cognitive Neural Mechanisms of Anaphor Processing During Language Comprehension.

Anaphora is an essential means of maintaining textual coherence, the phenomenon of replacing one word or phrase in the preceding part of a discourse with another. At least two crucial stages are involved in anaphor processing: bonding and resolution. The links between the anaphor and potential antecedents are established in the former stage, which would be evaluated and integrated into the latter stage. We reviewed relevant event-related potential (ERP) studies that examined the time course of anaphor processing and neural oscillation studies that explored energy changes in alpha, theta, and gamma frequency bands, which were associated with attention, working memory retrieval, and integration, respectively. The existing neuroimaging studies revealed the involvement of language processing networks and the Theory of Mind (ToM). Further research should explore the neural correlates and the effects of potential factors on anaphor processing, which could help gain a more comprehensive picture from multiple perspectives.

Neutralizing antibodies and T-cell responses to inactivated SARS-CoV-2 vaccine in COVID-19 convalescents one and a half years after infection.

Vaccines have been considered the most promising solution for ending the coronavirus disease 2019 (COVID-19) pandemic. Information regarding neutralizing antibodies (NAbs) and T-cell immune response in inactivated SARS-CoV-2 vaccine-immunized COVID-19 convalescent patients were either only available for a short time after illness recovered or not available at all (T-cell immunity). We evaluated SARS-CoV-2 NAbs and cellular immune responses to the SARS-CoV-2 inactivated vaccine in convalescent patients who recovered from infection for about one and a half years. We found that compared to before vaccination, SARS-CoV-2 NAbs and specific T-cell responses were significantly boosted by the inactivated vaccine in convalescent patients, which confirmed the pre-existing adaptive immunity in SARS-CoV-2 infected people. We observed that NAbs and IFN-γ-secreting T-cell response elicited by a single vaccine dose in subjects with prior COVID-19 infection were higher than after two doses of vaccine in SARS-CoV-2 naïve subjects. Both humoral and cellular immune responses elicited by one and two doses of inactivated vaccine were comparable in COVID-19-recovered persons. In conclusion, inactivated COVID-19 vaccine induced robust NAbs and T-cell responses to SARS-CoV-2 in COVID-19 convalescent patients and immune responses after one dose were equal to that after receiving two doses, which highlighted that robust humoral and cellular immune response can be reactivated by the inactivated vaccine in SARS-CoV-2 convalescent patients.

Cochlear implantation in a patient with congenital microtia, cochlear hypoplasia, venous anomalies of the temporal bone and laryngomalacia: Challenges and surgical considerations.

RATIONALE AND PATIENT CONCERNS: Congenital hearing loss is often caused by an inner ear malformation, in such cases, the presence of other anomalies, such as microtia, and venous anomalies of the temporal bone and laryngomalacia makes it challenging to perform cochlear implantation surgery. DIAGNOSES: This study reports the case of a 28-month-old girl with congenital profound hearing loss, laryngomalacia, and malformed inner ear, who received cochlear implantation surgery. The bony structure, vessels and nerves were first assessed through magnetic resonance imaging and computed tomography before exploring the genetic basis of the condition using trio-based whole exome sequencing. Perioperative evaluation and management of the airway was then performed by experienced anesthesiologist, with the surgical challenges as well as problems encountered fully evaluated. INTERVENTIONS: Cochlear implantation was eventually performed using a trans-mastoid approach under uneventful general anesthesia. OUTCOMES: Due to the small size of the cochlea, a short electrode FLEX24 was inserted through the cochleostomy. LESSONS: Considering the high risk of facial nerve injury and limited access to the cochlea when patients present significant bony and venous anomalies, cochlear implantation in such patients require careful preoperative evaluation and thoughtful planning. In these cases, airway assessment, magnetic resonance venography, magnetic resonance arteriography, and magnetic resonance imaging and computed tomography can be useful to minimize the risks. Intraoperative facial nerve monitoring is also recommended to assist in the safe location of facial nerve.

Aggregation of pre-implantation embryos improves establishment of parthenogenetic stem cells and expression of imprinted genes.

Parthenogenetic embryonic stem cells (PgES) might advance cell replacement therapies and provide a valuable in vitro model system to study the genomic imprinting. However, the differential potential of PgES cells was limited. It could result from relative low heterology of PgES cells compared with ES cells from fertilization (fES), which produce different expression of most imprinted genes. Here, we described the establishment of PgES cells by aggregating parthenogenetic embryos at the 8-cell stage (aPgES cells), which may increase heterozygy. We found that derivation of aPgES cells in association with an increased number of inner cell mass cells by aggregating was more efficient than that of PgES cells from a single parthenogenetic blastocyst. The aPgES cells have normal karyotype, stain positive for alkaline phosphatase, express high levels of ES cell markers and can differentiate into teratomas composed of the three germ layers. Moreover, compared with PgES cells, the more highly upregulated paternally expressed imprinted genes were observed in aPgES cells, the same change was not shown in aPg blastocysts. This suggested that the aggregation induced effect could modify the expression of paternally expressed imprinted genes. Our studies showed that aPgES cells, the expression of imprinted genes in which more closely resemble fES cells than PgES cells, would contribute to all organs and avoiding immuno-rejection, which may provide invaluable material for regeneration medicine.

Cytochalasin B treatment of mouse oocytes during intracytoplasmic sperm injection (ICSI) increases embryo survival without impairment of development.

Intracytoplasmic sperm injection (ICSI) is a technique commonly used in clinical and research settings. In mouse oocytes, conventional ICSI has a poor survival rate caused by a high level of lysis. Cytochalasin B (CB) is a toxic microfilament-inhibiting agent that is known to relax the cytoskeleton and enhance the flexibility of oocytes. CB has been used widely in nuclear transfer experiments to improve the success rate of the micromanipulation, however information describing the use of CB in ICSI is limited. Here, we demonstrated that the addition of 5 µg/ml CB to the manipulation medium of ICSI procedure significantly improved the survival rate of the ICSI embryos (80.74% vs. 89.50%, p < 0.05), and that there was no harm for the in vitro or in vivo development. The birth rates and birth weights were not significantly different between the CB-treated and -untreated groups. Interestingly, the microfilaments of the ICSI embryos were almost undetectable immediately after CB treatment; however, they gradually re-appeared and had fully recovered to the normal level 2 h later. Moreover, CB did not disturb spindle rotation, second polar body formation or pronuclei migration, and had no effect on the microtubules. We thus conclude that ICSI manipulation in CB-containing medium results in significantly improved survival rate of mouse ICSI embryos, and that short-term treatment with CB during ICSI manipulation does not have adverse effects on the development of ICSI embryos.

Unity of heaven and humanity: Mediating role of the relational-interdependent self in the relationship between Confucian values and holistic thinking.

As the primary value system in Chinese culture for almost 2,000 years, Confucianism has profoundly influenced the mindset of Chinese people. Cultural psychology studies have highlighted that individuals with different cultural backgrounds vary in their preferences for certain personality traits, such as self-construal, and their metacognitive characteristics, such as thinking modes. Compared with Western cultures, Chinese culture shows a preference for the interdependent self and holistic thinking. To investigate the relationship between the relational-interdependent self, holistic thinking, and traditional Chinese values (which are represented by Confucian values), we surveyed 327 Chinese adults using the Confucian Traditional Values Survey, Holistic Thinking Scale, and Relational-Interdependent Self-Construal Scale. The results show that Confucian values positively influence both holistic thinking and the relational-interdependent self, the latter of which partially mediates the positive relationship between Confucian values and holistic thinking. This study deepens the understanding of the psychological features of Chinese culture.

Efficacy and safety of induction chemotherapy with daunorubicin or idarubicin in the treatment of an adult with acute lymphoblastic leukemia.

BACKGROUND: Anthracyclines are dispensable components of chemotherapy of patients with acute lymphoblastic leukemia (ALL). OBJECTIVE: To analyze the efficacy and safety of induction with idarubicin (IDA) or liposoma daunorubicin (L-DNR) in treatment of adults with high-risk ALL (HR-ALL) (presence of mixed lineage leukemia gene [MLL] rearrangements, t[1;19], or prednisone poor response). METHODS: Among 58 enrolled patients, 29 cases were defined as the IDA group and the other 29 patients were put into the L-DNR group. Both overall survival (OS) and progression-free survival (PFS) were estimated and overall response rate (ORR) was compared between the groups. RESULTS: The L-DNR group's OS and PFS were insignificantly higher than in the IDA group (P=0.261 and P=0.247). Although not significantly different, the ORR of adults with HR-ALL receiving L-DNR regimens was also higher than in the IDA group (P=0.085). Comprehensive cytogenetic analysis revealed that patients harboring MLL rearrangement, E2A-PBX1, and P53 mutation had poorer prognosis than others. All 58 patients experienced hematologic response in this study; however, the length of hematologic response in the IDA group was significantly longer than in the L-DNR group (P=0.005). The incidence of bleeding and infection was without significant difference between the groups (both P>0.05). CONCLUSION: L-DNR proved to be an effective drug within a multiagent approach, which shows a favorable overall profile, as well as similar adverse events when compared with IDA in HR-ALL. Patients with E2A-PBX1 are much more sensitive to L-DNR than IDA. Despite some progress made, outcomes in MLL rearrangement or P53 mutation carriers remain unsatisfactory, and intensive treatment will be critical.

Influence of Confucianism and Taoism on self-construal and thinking style: an intervention study.

Using original texts of Confucian and Taoist primary classics as materials, we conducted an eight-week educational intervention experiment combining classroom teaching and post-class reflection as cultural manipulation. Ninety-four sixth-grade students from three parallel mainstream classes were randomly assigned to three intervention groups, comprising two experimental groups (Confucian and Taoist values interventions) and a control group (natural science intervention). The results suggest that the Confucian intervention had a positive effect on interdependent self and holistic thinking, the Taoist intervention had a positive effect on independent self and holistic thinking, and the natural science intervention promoted analytical thinking.

CRISPR/Cas9-Based Genome Editing and Its Application in Aspergillus Species.

Aspergillus, a genus of filamentous fungi, is extensively distributed in nature and plays crucial roles in the decomposition of organic materials as an important environmental microorganism as well as in the traditional fermentation and food processing industries. Furthermore, due to their strong potential to secrete a large variety of hydrolytic enzymes and other natural products by manipulating gene expression and/or introducing new biosynthetic pathways, several Aspergillus species have been widely exploited as microbial cell factories. In recent years, with the development of next-generation genome sequencing technology and genetic engineering methods, the production and utilization of various homo-/heterologous-proteins and natural products in Aspergillus species have been well studied. As a newly developed genome editing technology, the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system has been used to edit and modify genes in Aspergilli. So far, the CRISPR/Cas9-based approach has been widely employed to improve the efficiency of gene modification in the strain type Aspergillus nidulans and other industrially important and pathogenic Aspergillus species, including Aspergillus oryzae, Aspergillus niger, and Aspergillus fumigatus. This review highlights the current development of CRISPR/Cas9-based genome editing technology and its application in basic research and the production of recombination proteins and natural products in the Aspergillus species.

Neutralizing antibodies and cellular immune response after two doses of inactivated SARS-CoV-2 vaccine in China.

BACKGROUND: As of 2022, inactivated SARS-CoV-2 vaccines had been used in more than 91 countries. However, limited real world information was available on the immune responses of the inactivated SARS-CoV-2 vaccine. METHODS: We used SARS-CoV-2 pseudovirues to determine the neutralizing antibodies (NAbs) to wild type and several global variants and utilized enzyme-linked immunosorbent assay to investigate IFN-γ-secreting T-cell responses to SARS-CoV-2 among 240 vaccinated individuals after two doses of inactivated vaccine in China. RESULTS: A majority of the vaccinated (>90%) developed robust NAbs and T-cell responses to SARS-CoV-2 in the first two months after the second dose. After six months, only 37.0% and 44.0% of vaccinees had NAbs and T-cell immunity to SARS-CoV-2, respectively. Immune serum retained most of its neutralizing potency against the Alpha and Iota variants, but lost significant neutralizing potency against the Beta, Kappa, Delta, and Omicron variants. Only 40% of vaccine-sera retained low-level neutralization activities to Omicron, with a 14.7-fold decrease compared to the wild type. CONCLUSION: The inactivated SARS-CoV-2 vaccine stimulated robust NAbs and T-cell immune responses in the first two months after the second dose but the immune effect dropped rapidly, highlighing that a third dose or additional booster immunizations may be required to boost immunity against SARS-CoV-2.

Krüppel-like factor 7 attenuates hippocampal neuronal injury after traumatic brain injury.

Our previous study has shown that the transcription factor Krüppel-like factor 7 (KLF7) promotes peripheral nerve regeneration and motor function recovery after spinal cord injury. KLF7 also participates in traumatic brain injury, but its regulatory mechanisms remain poorly understood. In the present study, an HT22 cell model of traumatic brain injury was established by stretch injury and oxygen-glucose deprivation. These cells were then transfected with an adeno-associated virus carrying KLF7 (AAV-KLF7). The results revealed that, after stretch injury and oxygen-glucose deprivation, KLF7 greatly reduced apoptosis, activated caspase-3 and lactate dehydrogenase, downregulated the expression of the apoptotic markers B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and cleaved caspase-3, and increased the expression of ßIII-tubulin and the antiapoptotic marker Bcl-2. Furthermore, KLF7 overexpression upregulated Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) phosphorylation in HT22 cells treated by stretch injury and oxygen-glucose deprivation. Immunoprecipitation assays revealed that KLF7 directly participated in the phosphorylation of STAT3. In addition, treatment with AG490, a selective inhibitor of JAK2/STAT3, weakened the protective effects of KLF7. A mouse controlled cortical impact model of traumatic brain injury was then established. At 30 minutes before modeling, AAV-KLF7 was injected into the ipsilateral lateral ventricle. The protein and mRNA levels of KLF7 in the hippocampus were increased at 1 day after injury and recovered to normal levels at 3 days after injury. KLF7 reduced ipsilateral hippocampal atrophy, decreased the injured cortex volume, downregulated Bax and cleaved caspase-3 expression, and increased the number of 5-bromo-2'-deoxyuridine-positive neurons and Bcl-2 protein expression. Moreover, KLF7 transfection greatly enhanced the phosphorylation of JAK2 and STAT3 in the ipsilateral hippocampus. These results suggest that KLF7 may protect hippocampal neurons after traumatic brain injury through activation of the JAK2/STAT3 signaling pathway. The study was approved by the Institutional Review Board of Mudanjiang Medical University, China (approval No. mdjyxy-2018-0012) on March 6, 2018.