Multiparameter Assessment of Foam Cell Formation Progression Using a Dual-Color Switchable Fluorescence Probe.

The assessment of atherosclerosis (AS) progression has emerged as a prominent area of research. Monitoring various pathological features of foam cell (FC) formation is imperative to comprehensively assess AS progression. Herein, a simple benzospiropyran-julolidine-based probe, BSJD, with switchable dual-color imaging ability was developed. This probe can dynamically and reversibly adjust its molecular structure and fluorescent properties in different polar and pH environments. Such a polarity and pH dual-responsive characteristic makes it superior to single-responsive probes in dual-color imaging of lipid droplets (LDs) and lysosomes as well as monitoring their interaction. By simultaneously tracking various pathological features, including LD accumulation and size changes, lysosome dysfunction, and dynamically regulated lipophagy, more comprehensive information can be obtained for multiparameter assessment of FC formation progression. Using BSJD, not only the activation of lipophagy in the early stages and inhibition in the later phases during FC formation are clearly observed but also the important roles of lipophagy in regulating lipid metabolism and alleviating FC formation are demonstrated. Furthermore, BSJD is demonstrated to be capable of rapidly imaging FC plaque sites in AS mice with fast pharmacokinetics. Altogether, BSJD holds great promise as a dual-color organelle-imaging tool for investigating disease-related LD and lysosome changes and their interactions.

Allosteric Activator-Regulated CRISPR/Cas12a System Enables Biosensing and Imaging of Intracellular Endogenous and Exogenous Targets.

Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.

Intravascular papillary endothelial hyperplasia of the spleen in a child: a case report.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a vascular tumor characterized by the proliferation of endothelial cells with papillary formation. It is a rare benign condition affecting the head and neck. Currently, no cases of IPEH of the spleen have been reported. Here, we report a case of IPEH of the spleen in a child and discuss its clinical manifestations, imaging features, and surgical treatment. CASE PRESENTATION: A 5-year-old female presented with a 4-month-old tumor in the left upper abdomen, abdominal pain, and constipation. She underwent radiography, barium enema, US, and MRI. A solid space-occupying mass was found in the left abdominal cavity on preoperative imaging, and it was diagnosed as angiosarcoma. The lesion was surgically resected. Histopathological analysis was consistent with IPEH. CONCLUSION: Clinicians should consider the possibility of IPEH in patients presenting with tumors in the spleen, which is curable by surgical resection. Malignant vascular tumors must be excluded in the differential diagnosis of IPEH to prevent misdiagnosis and inappropriate overtreatment.

Synthesis of novel 3/5(3,5)-(di)nitropaeonol hydrazone derivatives as nematicidal agents.

Eighteen novel 3/5(3,5)-(di)nitropaeonol hydrazone derivatives were prepared, and their structures well characterized by 1H NMR, HRMS, and mp. Due to the steric hindrance, the substituents on the C = N double bond of all hydrazine compounds (except E/Z = 4/1 for IV-1g, IV-1l, IV-2b, and E/Z = 3/2 for IV-1n, IV-3a) adopted E configuration. Among all compounds, four compounds 2, 4, IV-1j, and IV-1n exhibited potent nematicidal activity than their precursor paeonol, especially 5-nitropaeonol (2) and 3,5-dinitropaeonol (4) displayed the most potent nematicidal activity Heterodera glycines in vivo with LC50 values of 32.3307 and 36.7074 mg/L, respectively.

Early argatroban and antiplatelet combination therapy in acute non-lacunar single subcortical infarct associated with mild intracranial atherosclerosis.

BACKGROUND: Patients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6-12 h after symptom onset is effective and safe in these patients is unknown. METHODS: A review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6-12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0-1 at 90 days) was estimated using multivariable logistic regression analysis. RESULTS: A total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P < 0.001). The relative risk (95% credible interval) for an mRS score improving from 0 to 1 in the argatroban group was 1.50 (1.05-2.70). END occurred in 10 (7.3%) patients in the argatroban group compared with 37 (22.0%) in the DAPT group (P < 0.001). No patients experienced symptomatic hemorrhagic transformation. CONCLUSIONS: Early combined administration of argatroban and an antiplatelet agent (aspirin or clopidogrel) may be beneficial for patients with non-lacunar SSI associated with mild ICAS identified by MRI screening and may attenuate progressive neurological deficits. TRIAL REGISTRATION: Our study is a retrospectively registered trial.

Cationic porphyrins with large side arm substituents as resonance light scattering ratiometric probes for specific recognition of nucleic acid G-quadruplexes.

Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique-resonance light scattering (RLS)-based ratiometric recognition. To achieve the RLS probing of G-quadruplexes in the important physiological pH range of 7.4-6.0, four water soluble cationic porphyrin derivatives, including an unreported octa-cationic porphyrin, with large side arm substituents were synthesized and developed as RLS probes. These RLS probes were demonstrated to work well for ratiometric recognition of G-quadruplexes with high specificity against single- and double-stranded DNAs, including long double-stranded ones. The working mechanism was speculated to be based on the RLS signal changes caused by porphyrin protonation that was promoted by the end-stacking of porphyrins on G-quadruplexes. This work adds an important member in G-quadruplex probe family, thus providing a useful tool for studies on G-quadruplex-related events concerning G-quadruplex formation, destruction and changes in size, shape and aggregation. As a proof-of-concept example of applications, the RLS probes were demonstrated to work well for label-free and sequence-specific sensing of microRNA. This work also provides a simple and useful way for the preparation of cationic porphyrins with high charges.

Synthesis, anti-oomycete activity, and SAR studies of paeonol derivatives.

Three series of sulfonate derivatives of paeonol were synthesized and screened in vitro for their anti-oomycete activity against P. capsici, respectively. Among all the compounds, 4m displayed the best promising and pronounced anti-oomycete activity against P. capsici than zoxamide, with the EC50 values of 24.51 and 26.87 mg/L, respectively. The results show that acetyl and 4-OCH3 are two necessary groups. The existence of these two sites is closely related to the anti-oomycete activity. Relatively speaking, hydroxyl group is well tolerated, and the results showed that after modification of hydroxyl group with sulfonyl, the anti-oomycete activity was significantly increased. [Formula: see text].

Safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine - a meta-analysis of randomized controlled trials.

AIM: To systematically evaluate the safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies from the results of randomized controlled trials. METHODS: Online databases were searched on calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine. Overall withdrawal, withdrawal due to adverse events, adverse events, serious adverse events and specific adverse events were extracted from the included studies. A meta-analysis was performed with Revman 5.3.0 software. RESULTS: Ten studies that investigated four drugs (galcanezumab, erenumab, fremanezumab and eptinezumab) with 5817 participants were included in this study. Serious adverse events, overall withdrawals, withdrawal due to adverse events and any adverse events were not significantly associated with monoclonal antibody treatment. Injection site pain and erythema were significantly higher in the calcitonin-gene-related peptide binding monoclonal antibodies treatment group than in the placebo group. The rates of serious adverse events were significantly higher in the galcanezumab 120 mg group. Injection site erythema was associated with galcanezumab 120 mg and 240 mg. Injection site pain and nasopharyngitis were associated with galcanezumab 150 mg and 5 mg, respectively. Overall adverse events were significantly higher with erenumab 70 mg and 140 mg. Treatment-related adverse events were significantly higher with fremanezumab 225 mg/month and 675 mg/quarter. CONCLUSIONS: This study provides data on the safety and tolerability profiles of calcitonin-gene-related peptide binding monoclonal antibodies and confirms their potential use as preventive treatments for episodic migraine. In addition to the acceptable withdrawal rates, serious adverse events were rare, and the severity of most adverse events was mild to moderate. Injection site reaction may be the major adverse event associated with galcanezumab.

Validation of the Neurological Disorders Depression Inventory for Epilepsy (NDDIE) as a rapid suicidality screening tool in Chinese people with epilepsy.

OBJECTIVE: The objective of this study was to validate the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (NDDIE) as a suicidality screening tool in Chinese people with epilepsy (PWE). METHODS: A consecutive cohort of PWE was recruited from West China Hospital and 363 Hospital. Each patient received a psychiatric evaluation with the Mini International Neuropsychiatric Interview (MINI) and the Chinese version of the NDDIE (C-NDDIE). Demographic and clinical characteristics were collected. Receiver operating characteristic (ROC) curve analysis was conducted. The best possible cutoff was identified with the highest Youden index. Specificity, sensitivity, positive, and negative predictive values were calculated. RESULTS: Among a total of 355 participants, 41 (11.5%) had a moderate to high suicide risk according to the Suicidality Module (SM) of the MINI. Receiver operating characteristic (ROC) curve analysis showed that item 4 ("I'd be better off dead") of the NDDIE had an area under the curve (AUC) of 0.930 (95% confidence interval [CI] = 0.884-0.977), a sensitivity of 80.5%, a specificity of 94.9%, a positive predictive value (PPV) of 68.0%, a negative predictive value (NPV) of 97.7%, and the largest Youden index of 0.754 for a cutoff score of >2. CONCLUSION: Item 4 of the NDDIE is a valuable tool for screening suicidality in Chinese PWE.

Curcumin intervention for cognitive function in different types of people: A systematic review and meta-analysis.

Curcumin is a polyphenolic natural compound with diverse and attractive biological activities, which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia, or mood disorders. However, clinical trials and animal studies have yielded conflicting conclusions regarding its effectiveness for cognition in different individuals. The aim of this review is to meta-analytically assess the effectiveness of curcumin for cognitive function in different types of people. A preliminary search on PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang Data and China Biology Medicine disc was performed to identify randomized controlled trials investigating the effect of curcumin on cognition. Six clinical trials with a total of 289 subjects met inclusion criteria for this review. We used a random-effects model to calculate the pooled standardized difference of means (SMD). For older adults who received curcumin, scores on measures of cognitive function (SMD = 0.33, 95% confidence interval [CI] [0.05, 0.62]; p = 0.02), occurrence of adverse events (odds ratio [OR] = 5.59, 95% CI [0.96, 36.80]; p = 0.05), and measures of depression (SMD = -0.29, 95% CI [0.64, 0.05]; p = 0.09) indicated significant memory improvement. In patients with Alzheimer's disease (AD), scores in measures of cognition status (SMD = -0.90, 95% CI [1.48, -0.32]; p = 0.002) indicated that there was a trend for treated subjects to do worse than placebo-treated subjects on the Mini-Mental State Examination. The occurrence of adverse events (OR = 0.87, 95% CI [0.10, 7.51]; p = 0.90) was similar to those who received placebo. Due to insufficient data, it was impossible to provide a narrative account of only the outcomes for schizophrenia. Curcumin appears to be more effective in improving cognitive function in the elderly than in improving symptoms of AD and schizophrenia. Curcumin is also safe and tolerated among these individuals. Because of the small number of studies available, a funnel plot or sensitivity analysis was not possible. Further high-quality trials with larger sample sizes or bioavailability-improved curcumin formulations may be considered for reliable assessment.

Aerobic Exercise Intervention Alters Executive Function and White Matter Integrity in Deaf Children: A Randomized Controlled Study.

This study examined the effects of an 11-week aerobic exercise intervention on executive function (EF) and white matter integrity (WMI). In total, 28 deaf children (aged 9-13 years) were randomly assigned to either an 11-week exercise intervention or the control group. All the children had behavioral assessment and diffusion tensor imaging prior to and following the exercise intervention. The behavioral performance results demonstrated that EF was enhanced by exercise. Relative to the control group, WMI of the exercise intervention group showed (1) lower fractional anisotropy (FA) in the pontine crossing tract (PCT) and right cingulum (hippocampus) (CH), genu of the corpus callosum (gCC), right inferior cerebellar peduncle (ICP), left superior corona radiata (SCR), and left superior frontooccipital fasciculus (SFOF); (2) higher mean diffusivity (MD) in the gCC, right CH, right inferior frontooccipital fasciculus (IFOF), and left anterior limb of the internal capsule (ALIC); and (3) lower MD in the left ICP and left tapetum (TAP). Furthermore, the lower FA in gCC showed a significant negative correlation with improvement in behavioral performance, but the correlation was not significant after FDR correction. These results suggest that exercise can effectively improve deaf children's EF and reshape the WMI in deaf children. The improved EF by exercise is not related to a reshaping of WMI, but more studies on the relationship between EF and WMI by exercise may be needed.

Water-Soluble Cationic Metalloporphyrins: Specific G-Quadruplex-Stabilizing Ability and Reversible Chirality of Aggregates Induced by AT-Rich DNA.

Cu-TMPipPrOPP and Zn-TMPipPrOPP, two new cationic metallo derivatives of TMPipPrOPP (5,10,15,20-tetrakis{4-[3-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin), a porphyrin with four bulky side chains, were synthesized and characterized. The interactions of the new metalloporphyrins with structurally different DNAs were then compared with those of TMPipPrOPP. The introduction of bulky side chains provides the porphyrin derivatives with excellent binding specificity for G-quadruplex DNA, which is reflected by (1) the significantly different optical responses of TMPipPrOPP toward G-quadruplexes in comparison with single-stranded and duplex DNAs and (2) the ability of the three porphyrin derivatives to effectively stabilize G-quadruplexes, with no or little effect on the stability of duplex DNA. TMPipPrOPP can achieve colorimetric and fluorescent discrimination of G-quadruplexes from single-stranded and duplex DNAs with extraordinary high specificity. Due the presence of metal ions, Cu-TMPipPrOPP and Zn-TMPipPrOPP are deprived of the ability for optical G-quadruplex recognition but show enhanced ability to stabilize G-quadruplexes. In addition, because of the presence of the four cationic side chain substituents, the three porphyrin derivatives can form chiral aggregates via electrostatic interactions along the surface of structurally diverse DNAs. The chirality of aggregates formed by TMPipPrOPP is not changed by the nature of the template DNAs, whereas aggregates formed by Cu-TMPipPrOPP and Zn-TMPipPrOPP in the presence of adenine-thymine (AT) rich duplex DNA show completely inverted chirality in comparison with those formed in the presence of other DNAs. Interestingly, the chirality of the aggregates can be reversibly switched many times by alternating the ratio of Cu-TMPipPrOPP (or Zn-TMPipPrOPP) to AT-rich duplex DNA.

[Association between IL-6 C-572G and susceptibility to spontaneous preterm birth].

OBJECTIVE: To investigate the association between the genetic polymorphism of IL-6 C-572G and susceptibility to spontaneous preterm birth (SPTB). METHODS: The subjects were from Beijing and the surrounding areas of Beijing. This case-control study enrolled 569 SPTB infants, including 56 extremely preterm (<28 weeks of gestation), 166 very preterm (28-31+6 weeks of gestation) and 347 moderate to late preterm infants (32 to 36+6 weeks of gestation). A total of 673 term infants were enrolled as the control group. The latest Sequenom MassARRAY®SNP detection technique was used for the typing of single nucleotide polymorphism of IL-6 C-572G. RESULTS: Compared with the CC genotypes, the IL-6 C-572G G-positive genotype (CG+GG genotype) was significantly associated with an increased susceptibility to moderate to late SPTB (OR=1.35, 95%CI: 1.01-1.80, P=0.04). CONCLUSIONS: Among the Chinese population, IL-6 C-572G polymorphism is associated with susceptibility to moderate to late SPTB.

CHHBP: a newly identified receptor of crustacean hyperglycemic hormone.

Crustacean hyperglycemic hormone (CHH) is a neurohormone found only in arthropods that plays a pivotal role in the regulation of hemolymph glucose levels, molting and stress responses. Although it was determined that a membrane guanylyl cyclase (GC) acts as the CHH receptor in the Y-organ during ecdysteroidogenesis, the identity of the CHH receptor in the hepatopancreas has not been established. In this study, we identified CHH binding protein (CHHBP), as a potential receptor by screening the annotated unigenes from the transcriptome of ITALIC! Eriocheir sinensis, after removal of the eyestalk. Analysis of the binding affinity between CHH and CHHBP provided direct evidence that CHH interacts with CHHBP in a specific binding mode. Subsequent analysis showed that CHHBP is expressed primarily in the hepatopancreas where it localizes to the cell membrane. In addition, real-time PCR analysis showed that ITALIC! CHHBPtranscript levels gradually increase in the hepatopancreas following eyestalk ablation. RNAi-mediated suppression of ITALIC! CHHBPexpression resulted in decreased glucose levels. Furthermore, the reduction of blood glucose induced by ITALIC! CHHBPRNAi reached the same level as that observed in the eyestalk ablation group, suggesting that CHHBP is involved in glucose metabolism regulated by CHH. In addition, compared with the control group, injection of CHH was unable to rescue the decreased glucose levels in ITALIC! CHHBPRNAi crabs. CHH induced transport of 2-NBDG to the outside of cells, with indispensable assistance from CHHBP. Taken together, these findings suggest that CHHBP acts as one type of the primary signal processor of CHH-mediated regulation of cellular glucose metabolism.

Two cationic porphyrin isomers showing different multimeric G-quadruplex recognition specificity against monomeric G-quadruplexes.

Ligands that can interact specifically with telomeric multimeric G-quadruplexes could be developed as promising anticancer drugs with few side effects related to other G-quadruplex-forming regions. In this paper, a new cationic porphyrin derivative, m-TMPipEOPP, was synthesized and characterized. Its multimeric G-quadruplex recognition specificity under molecular crowding conditions was compared to its isomer p-TMPipEOPP. The slight structural difference accounts for different multimeric G-quadruplex recognition specificity for the two isomers. p-TMPipEOPP can barely discriminate between multimeric and monomeric G-quadruplexes. By contrast, m-TMPipEOPP can bind with multimeric but not with monomeric G-quadruplexes. p-TMPipEOPP might bind to multimeric G-quadruplexes by two modes: sandwich-like end-stacking mode and pocket-dependent intercalative mode. Increasing the pocket size between adjacent two G-quadruplex units is beneficial for the latter mode. m-TMPipEOPP might bind to multimeric G-quadruplexes by a side binding mode, which confers m-TMPipEOPP with higher multimeric G-quadruplex recognition specificity compared to p-TMPipEOPP. m-TMPipEOPP increases the stability of multimeric G-quadruplex under both dilute and molecular crowding conditions but its G-quadruplex-stabilizing ability is a little weaker than p-TMPipEOPP. These results provide important information for the design of highly specific multimeric G-quadruplex ligands. Another interesting finding is that pocket size is an important factor in determining the stability of multimeric G-quadruplexes.

[Folic acid modified polyrotaxanes effectively transfer si RNA-CD47 to inhibit the proliferation of melanoma].

To investigate the effect that folic acid-modified polyrotaxanes(FPP) transfered siRNA CD47 to inhibit melanoma proliferation, the expression of CD47 in clinical melanoma patients was tested by Western blot and RT-PCR, respectively. Physical performance of FPP(siRNA-CD47: CD47) nanoparticles was tested by Malvern particle size instrument and scanning electron microscope. The clone formation experiment demonstrated that FPP(CD47) nanoparticles inhibited the growth of clones. Invasion assay revealed that FPP(CD47) inhibited migration of B16F10 cells. Tumor bearing mice were used in the experiment to test the efficacy of FPP(CD47) treatment. Compared with the control group, high expression of CD47 was observed in the clinical melanoma patients. FPP(CD47) nanoparticle size at 80 nm exhibited a potential of 10 m V; compared with FPP(Con), fluorescence intensity was significantly reduced to 4.2% and B16F10 cell clone formation was decreased by 91% in the FPP(CD47) treatment. Tumor volume of tumor-burdened mice was decreased by 90% with FPP(CD47) treatment. FPP(CD47) lowered CD47 protein and m RNA expression in the tumor. This study suggests that FPP may transfer siRNA CD47 into the cancer cells to inhibit melanoma growth effectively.

[Association between tumor necrosis factor-α G-308A polymorphisms and genetic susceptibility to spontaneous preterm birth].

OBJECTIVE: To study the association between tumor necrosis factor-α (TNF-α) G-308A polymorphisms and genetic susceptibility to spontaneous preterm birth (SPTB). METHODS: The case group enrolled 753 SPTB infants and the control group included 681 term infants. TNF-α G-308A polymorphisms were genotyped using Sequenom MassARRAY®SNP. RESULTS: The frequencies of the allele (G and A) in the case and control groups were not significantly different (P=0.35). The frequencies of the genotypes (GG, GA and AA) in the case and control groups were not significantly different (P=0.64). The logistic regression analysis found that TNF-α G-308A was not associated with genetic susceptibility to SPTB (OR=0.85; 95%CI: 0.61-1.19; P=0.35). CONCLUSIONS: There is no association between the polymorphisms of TNF-α G-308A and the genetic susceptibility to SPTB.

[Association between interleukin-1ß C+3953T and genetic susceptibility to spontaneous preterm birth: a case-control study].

OBJECTIVE: To study the association between interleukin-1ß (IL-1ß) C+3953T and genetic susceptibility to spontaneous preterm birth (SPTB). METHODS: In this case-control study, 753 SPTB neonates were enrolled in the case group and 681 full-term neonates were enrolled in the control group. The latest Sequenom MassARRAY®SNP detection technique was used for the typing of single nucleotide polymorphisms (SNP) of IL-1ß C+3953T. RESULTS: Compared with those carrying CC genotype of IL-1ß C+3953T, the neonates who carried at least one T allele (CT+TT genotype) had significantly increased risks of SPTB, SPTB complicated by premature rupture of membranes, and mild preterm birth. CONCLUSIONS: In the Chinese population, IL-1ß C+3953T has significant genetic association with an increased risk of SPTB. The identification of this SNP helps to prevent SPTB and clarify the causes and pathogenesis of SPTB.

Specific recognition and stabilization of monomeric and multimeric G-quadruplexes by cationic porphyrin TMPipEOPP under molecular crowding conditions.

Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under dilute conditions. Living cells are crowded with biomacromolecules, and the ≈ 200-nucleotide G-rich single-stranded overhang of human telomeric DNA has the potential to fold into multimeric G-quadruplex structures containing several G-quadruplex units. Studies on interactions between ligands and multimeric G-quadruplexes under molecular crowding conditions could provide a new route for screening specific telomeric G-quadruplex-targeting ligands. Herein, TMPipEOPP, a cationic porphyrin derivative designed by us, was demonstrated as a promising multimeric telomeric G-quadruplex ligand under molecular crowding conditions. It could highly specifically recognize G-quadruplexes. It could also promote the formation of G-quadruplexes and stabilize them. Detailed studies showed that TMPipEOPP interacted with monomeric G-quadruplexes in sandwich-like end-stacking mode of quadruplex/TMPipEOPP/quadruplex and interacted with multimeric human telomeric G-quadruplexes by intercalating into the pocket between two adjacent G-quadruplex units. The pocket size greatly affected TMPipEOPP binding. A larger pocket was advantageous for the intercalation of TMPipEOPP. This work provides new insights into the ligand-binding properties of multimeric G-quadruplexes under molecular crowding conditions and introduces a new route for screening anticancer drugs targeting telomeric G-quadruplexes.

[Analysis of MLC1 gene mutation in a Chinese family with megalencephalic leukoencephalopathy with subcortical cysts].

The clinical data of a patient with megalencephalic leukoencephalopathy (MLC) with subcortical cysts and her parents were collected. MLC1 gene mutation was detected by polymerase chain reaction and direct DNA sequencing. The patient presented with motor developmental delay and giant skull, and brain magnetic resonance imaging showed diffuse white matter swelling accompanied by subcortical cysts in bilateral frontal and parietal lobes. Gene sequencing identified two heterozygous mutations of MLC1, including missense mutation in exon 3 (c.217G>A, p.Gly73Arg) and splice site mutation in intron 9 (c.772-1G>C in IVS9-1). The patient's parents both had heterozygous mutation c.772-1G>C in IVS9-1 with normal phenotype. It can be presumed that c.772-1G>C in IVS9-1 comes from the parents, and c.217G>A (p.Gly73Arg) is a de novo mutation.