Strategy to Efficient Photodynamic Therapy for Antibacterium: Donor-Acceptor Structure in Hydrogen-Bonded Organic Framework.

While the construction of a donor-acceptor (D-A) structure has gained great attention across various scientific disciplines, such structures are seldomly reported within the field of hydrogen-bonded organic frameworks (HOFs). Herein, a D-A based HOF is synthesized, where the adjacent D-A pairs are connected by hydrogen bonds instead of the conventionally employed covalent bonds. This structural feature imparts material with a reduced energy gap between excited state and triplet state, thereby facilitating the intersystem crossing (ISC) and boosting the generation rate of single oxygen (quantum yield = 0.98). Consequently, the resulting material shows high performance for antimicrobial photodynamic therapy (PDT). The impact of D-A moiety is evident when comparing this finding to a parallel study conducted on an isoreticular HOF without a D-A structure. The study presented here provides in-depth insights into the photophysical properties of D-A pair in a hydrogen-bonded network, opening a new avenue to the design of innovative materials for efficient PDT.

Removal of diclofenac sodium from water using a polyacrylonitrile mixed-matrix membrane embedded with MOF-808.

MOF-808, owing to the synergistic effect of its large surface area and surface charge matching, showed a diclofenac sodium (DCF) removal capacity as high as 630 mg g-1, and the ability to adsorb 436 mg g-1 DCF in two hours, outperforming many common Zr-MOFs under the same conditions. Importantly, a series of free-standing mixed-matrix membranes made by combining polyacrylonitrile with MOF-808 were fabricated and exhibited high efficiency of removing DCF from water via an easily accessible filtration method.

Corrigendum: Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance.

[This corrects the article DOI: 10.3389/fpsyt.2021.679206.].

Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance.

Heroin use disorder is a chronic and relapsing disease that induces persistent changes in the brain. The diagnoses of heroin use disorders are mainly based on subjective reports and no valid biomarkers available. Recent researches have revealed that circulating miRNAs are useful non-invasive biomarkers for diagnosing brain diseases such as Alzheimer's disease, multiple sclerosis, schizophrenia, and bipolar disorder. However, studies on circulating miRNAs for the diagnosis of heroin use disorders are rarely reported. In this study, we investigated the differential expression of plasma miRNAs in 57 heroin-dependent patients. Based on literature research and microarray analysis, two candidate miRNAs, miR-320a and let-7b-5p, were selected and analyzed by quantitative real-time RT-PCR. The results showed miR-320a and let-7b were significantly upregulated in plasma of the heroin-dependent patients compared to that in healthy controls. The area under curves (AUCs) of receiver operating characteristic (ROC) curves of miR-320a and let-7b-5p were 0.748 and 0.758, respectively. The sensitivities of miR-320a and let-7b-5p were 71.9 and 70.2%, while the specificities of miR-320a and let-7b-5p were 76.1 and 78.3%, respectively. The combination of these two miRNAs predicted heron dependence with an AUC of 0.782 (95% CI 0.687-0.876), with 73.7% sensitivity and 82.6% specificity. Our findings suggest a potential use for circulating miRNAs as biomarkers for the diagnosis of heroin abuse.

Increased expression of plasma hsa-miR-181a in male patients with heroin addiction use disorder.

BACKGROUND: Drug addiction is an uncontrolled, chronic, and recurrent encephalopathy that presently lacks specific and characteristic biomarkers for diagnosis and treatment. As regulators of gene expression, microRNAs (miRNAs) are increasingly used for diagnostic and prognostic purposes in various disease states. Previous studies indicated that miRNAs play important roles in the development and progression of drug addictions, including addiction to methamphetamine, cocaine, alcohol, and heroin. METHODS: We identified significant miRNAs using the microarray method and then validated the hsa-miR-181a expression levels in 53 heroin addiction patients and 49 normal controls using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the potential associations between transcriptional levels in heroin addiction patients and their clinicopathological features were analyzed. RESULTS: A total of 2006 miRNAs were differentially expressed between heroin addiction patients and normal controls. The top 10 up-regulated miRNAs in patients were hsa-miR-21a, hsa-miR-181a, hsa-miR-4459, hsa-miR-4430, hsa-miR-4306, hsa-miR-22-3P, hsa-miR-486-5P, hsa-miR-371b-5P, hsa-miR-92a-3P, and hsa-miR-5001-5P. The top 10 down-regulated miRNAs in patients were hsa-miR-3195, hsa-miR-4767, hsa-miR-3135b, hsa-miR-6087, hsa-miR-1181, hsa-miR-4785, hsa-miR-718, hsa-miR-3141, hsa-miR-652-5P, and hsa-miR-6126. The expression level of hsa-miR-181a in heroin addiction patients was significantly increased compared with that in normal controls (P < .001). The area under the receiver operating characteristic curve of hsa-miR-181a was 0.783, the sensitivity was 0.867, and the specificity was 0.551. CONCLUSIONS: The increased expression of hsa-miR-181a in the plasma of heroin patients may be a consequence of the pathological process of heroin abuse. This study highlights the potential of hsa-miR-181a as a novel biomarker for the diagnosis of heroin addiction.

Biochemical Diagnosis in Substance and Non-substance Addiction.

An optimal biochemical marker for addiction would be some easily traced molecules in body specimens, which indicates indulgent addictive behaviors, or susceptibility to certain addictive stimuli. In this chapter, we discussed existing literature about possible biomarkers, and classified them into three categories: origin forms and metabolites of substances, markers from biochemical responses to certain addiction, and genetic and epigenetic biomarkers suggesting susceptibility to addiction. In every category, we examined studies concerning certain type of addiction one by one, with focuses mainly on opiates, psychostimulants, and pathological gambling. Several promising molecules were highlighted, including those of neurotrophic factors, inflammatory factors, and indicators of vascular injury, and genetic and epigenetic biomarkers such as serum miRNAs. DNA methylation signatures and signal nucleotide polymorphism of candidate gene underlying the addiction.

Experimental and mechanistic insights into copper(ii)-dioxygen catalyzed oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine and its derivatives.

A di-(2-pyridylmethyl)phenylamine ((PyCH2)2NPh) supported Cu(ii)/O2 catalytic system was explored with the synthesis of pyridylmethyl-based compounds of carboxylate (PyCOOH), amide (PyC(O)NHPh), and imine (PyCH[double bond, length as m-dash]NPh) from the oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine (PyCH2NHPh) and its derivatives, by means of controlling the addition of a base and/or water to the reaction system under a dioxygen atmosphere at room temperature. Experimental studies showed that the imine and amide species could be precursors in succession in the way to the final oxidation state of carboxylates. A cyclic catalytic mechanism was proposed including the base triggered C-H bond activation of the 2-pyridylmethyl group (PyCH2-) and the intermolecular Cu-OOH α-hydrogen atom abstraction from the coordinated imine substrate (PyCH[double bond, length as m-dash]NPh).

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

The protective effects of alpha-ketoacids against oxidative stress on rat spermatozoa in vitro.

The aim of this study was to determine the effects of antioxidants, including alpha-ketoacids (alpha-ketoglutarate and pyruvate), lactate and glutamate/malate combination, against oxidative stress on rat spermatozoa. Our results showed that H(2)O(2) (250 micromol L(-1))-induced damages, such as impaired motility, adenosine triphosphate (ATP) depletion, inhibition of sperm protein phosphorylation, reduced acrosome reaction and decreased viability, could be significantly prevented by incubation of the spermatozoa with alpha-ketoglutarate (4 mmol L(-1)) or pyruvate (4 mmol L(-1)). Without exogenous H(2)O(2) in the medium, the addition of pyruvate (4 mmol L(-1)) significantly increased the superoxide anion (O(2)(-).) level in sperm suspension (P < or = 0.01), whereas the addition of alpha-ketoglutarate (4 mmol L(-1)) and lactate (4 mmol L(-1)) significantly enhanced tyrosine-phosphorylated proteins with the size of 95 kDa (P < or = 0.04). At the same time, alpha-ketoglutarate, pyruvate, lactate, glutamate and malate supplemented in media can be used as important energy sources and supply ATP for sperm motility. In conclusion, the present results show that alpha-ketoacids could be effective antioxidants for protecting rat spermatozoa from H(2)O(2) attack and could be effective components to improve the antioxidant capacity of Biggers, Whitten and Whittingham media.

Dynamic regulation of glutamate decarboxylase 67 gene expression by alternative promoters and splicing during rat testis maturation.

Glutamate decarboxylase produces GABA, the main inhibitory neurotransmitter in adult mammalian brain. Two homologous forms of GAD encoded by separate genes have been identified in mammalian brain, with molecular weight of 67 kDa (GAD67) and 65 kDa (GAD65). Here, we studied the transcriptional regulation of GAD67. Three transcript variants (GAD67A, GAD67B, and GAD67C) transcribed from distinct categories of transcriptional start sites were identified. RT-PCR revealed these transcripts have distinct tissues distributions. Though GAD67A and GAD67B were co-expressed in brain and many nonneural tissues, in heart, only GAD67A was expressed. GAD67C was specifically expressed in testis. These transcripts also showed distinct developmental expression patterns during testis maturation. GAD67A was expressed at all age points examined. GAD67B was only detected at postnatal day 1 and day 5, while GAD67C was expressed from postnatal day 30. Characterizing the genome sequence upstream of transcriptional start sites of these transcripts revealed the presence of TATA-less promoters. Potential promoter activities were analyzed by coupling these promoter sequences to the open reading frame of a luciferase reporter gene in transient expression experiments. Moreover, our results showed GAD67 gene expression was also regulated by alternative splicing in postnatal day 1 and day 5 testis. The above results suggested GAD67 gene expression was dynamically regulated by alternative promoters and splicing during postnatal rat testis maturation.

Dynamic regulation of glutamic acid decarboxylase 65 gene expression in rat testis.

Glutamate decarboxylase 65 (GAD65) produces gamma-aminobutyric acid, the main inhibitory neurotransmitter in adult mammalian brain. Previous experiments, performed in brain, showed that GAD65 gene possesses two TATA-less promoters, although the significance is unknown. Here, by rapid amplification of cDNA ends method, two distinct GAD65 mRNA isoforms transcribed from two independent clusters of transcription start sites were identified in post-natal rat testis. RT-PCR results revealed that the two mRNA isoforms had distinct expression patterns during post-natal testis maturation, suggesting that GAD65 gene expression was regulated by alternative promoters at the transcription level. By using GAD65-specific antibodies, western blotting analysis showed that the 58-kDa GAD65, N-terminal 69 amino acids truncated form of full-length GAD65 protein, was developmentally expressed during post-natal testis maturation, suggesting that GAD65 gene expression in testis may also be regulated by post-translational processing. Confocal immunofluorescence microscopy revealed that GAD65 protein was presented in Leydig cells of Day 1 testis, primary spermatocytes and spermatids of postnatal of Day 90 testis. The above results suggested that GAD65 gene expression is dynamically regulated at multiple levels during post-natal testis maturation.

Utilization of an intron located polyadenlyation site resulted in four novel glutamate decarboxylase transcripts.

Glutamate decarboxylase (GAD) is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in central nervous system (CNS). Two homologous forms of GAD encoded by separate genes have been identified in mammalian brain, with molecular weight of 65 kDa (GAD65) and 67 kDa (GAD67). In the present study, four novel GAD67 transcripts produced by alternative splicing and polyadenlyation were cloned from rat testis. These novel GAD67 transcripts were widely expressed in non-neuronal tissues. During rat testis maturation, their expression level showed a time dependent change. These transcripts were predicted to synthesis of GAD proteins truncated of the binding site for pyridoxal phosphate, an essential cofactor, therefore cannot function as a decarboxylase. Thus, post-transcriptional processing mechanism as alternative splicing and polyadenlyation may play a crucial role in regulating rat GAD67 gene expression.

Identification and expression of GABAC receptor in rat testis and spermatozoa.

Our previous studies showed that gamma-aminobutyric acid (GABA)A and GABAB receptors are involved in rat sperm acrosome reaction induced by progesterone or GABA. Here, we report the presence of GABAC receptor in rat testis and spermatozoa. Full-length complementary DNA encoding the rho1, rho2 and rho3 subunits of GABAC receptor were cloned from rat testis; their sequences are identical to those of rat GABAC receptor in retina. Reverse transcription-polymerase chain reaction analysis showed that during the development of rat testis, the transcript levels of the rho1 and rho2 subunits showed little change, while the expression of rho3 was gradually up-regulated. Immunofluorescence analysis using an anti-rho1 antibody revealed that GABAC receptor exists on the elongated spermatid and sperm. Using a chlortetracycline assay, we found that N(4)-chloroacetylcytosine arabinoside, a GABAC receptor agonist, triggered rat sperm acrosome reaction; whereas (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid, a GABAC receptor antagonist, inhibited the ability of N(4)-chloroacetylcytosine arabinoside to induce acrosome reaction. These results suggested that GABAC receptors are also involved in rat sperm acrosome reaction.