Preimplantation genetic testing for monogenic disorders (PGT-M) offers an alternative strategy to prevent children from being born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes: a retrospective study.

BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) is now widely used as an effective strategy to prevent various monogenic or chromosomal diseases. MATERIAL AND METHODS: In this retrospective study, couples with a family history of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes and/or carrying the pathogenic genes underwent PGT-M to prevent children from inheriting disease-causing gene mutations from their parents and developing known genetic diseases. After PGT-M, unaffected (i.e., normal) embryos after genetic detection were transferred into the uterus of their corresponding mothers. RESULTS: A total of 43 carrier couples with the following hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes underwent PGT-M: Duchenne muscular dystrophy (13 families); methylmalonic acidemia (7 families); spinal muscular atrophy (5 families); infantile neuroaxonal dystrophy and intellectual developmental disorder (3 families each); Cockayne syndrome (2 families); Menkes disease, spinocerebellar ataxia, glycine encephalopathy with epilepsy, Charcot-Marie-Tooth disease, mucopolysaccharidosis, Aicardi-Goutieres syndrome, adrenoleukodystrophy, phenylketonuria, amyotrophic lateral sclerosis, and Dravet syndrome (1 family each). After 53 PGT-M cycles, the final transferable embryo rate was 12.45%, the clinical pregnancy rate was 74.19%, and the live birth rate was 89.47%; a total of 18 unaffected (i.e., healthy) children were born to these families. CONCLUSIONS: This study highlights the importance of PGT-M in preventing children born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes.

An injectable polyacrylamide/chitosan-based hydrogel with highly adhesive, stretchable and electroconductive properties loaded with irbesartan for treatment of myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) significantly contributes to the high incidence of complications and mortality associated with acute myocardial infarction. Recently, injectable electroconductive hydrogels (IECHs) have emerged as promising tools for replicating the mechanical, electroconductive, and physiological characteristics of cardiac tissue. Herein, we aimed to develop a novel IECH by incorporating irbesartan as a drug delivery system (DDS) for cardiac repair. Our approach involved merging a conductive poly-thiophene derivative (PEDOT: PSS) with an injectable dual-network adhesive hydrogel (DNAH) comprising a catechol-branched polyacrylamide network and a chitosan-hyaluronic acid covalent network. The resulting P-DNAH hydrogel, benefitting from a high conducting polymer content, a chemically crosslinked network, a robust dissipative matrix, and dynamic oxidation of catechol to quinone exhibited superior mechanical strength, desirable conductivity, and robust wet-adhesiveness. In vitro experiments with the P-DNAH hydrogel carrying irbesartan (P-DNAH-I) demonstrated excellent biocompatibility by cck-8 kit on H9C2 cells and a rapid initial release of irbesartan. Upon injection into the infarcted hearts of MIRI mouse models, the P-DNAH-I hydrogel effectively inhibited the inflammatory response and reduced the infarct size. In conclusion, our results suggest that the P-DNAH hydrogel, possessing suitable mechanical properties and electroconductivity, serves as an ideal IECH for DDS, delivering irbesartan to promote heart repair.

[Primary premature ejaculation of kidney deficiency and liver stagnation treated with warm acupuncture of large-quantity moxibustion: a randomized controlled trial].

OBJECTIVE: To explore the clinical effect of warm acupuncture with large-quantity moxibustion on primary premature ejaculation (kidney deficiency and liver stagnation). METHODS: A total of 240 patients with primary premature ejaculation (kidney deficiency and liver stagnation) were randomly divided into a warm acupuncture group (80 cases, 5 cases dropped out), an acupuncture group (80 cases, 4 cases dropped out) and a western medication group (80 cases, 6 cases dropped out). In the warm acupuncture group, a large quantity of moxibustion was delivered after acupuncture at Baihui (GV 20), Qihai (CV 6), Guanyuan (CV 4) and Zhongji (CV 3), as well as bilateral Fengchi (GB 20), lateral line 3 of forehead (MS 4), neishengzhiqi (TF2), Ganshu (BL 18), Shenshu (BL 23), and etc. One treatment with warm acupuncture took 40 min, once daily; five treatments were given per week and 4 weeks of treatment was required. In the acupuncture group, moxibustion was not delivered, and the rest operation of acupuncture was same as the warm acupuncture group. In the western medication group, dapoxetine hydrochloride tablets were administered orally, 30 mg each time, taken with warm water 1 h to 3 h before sexual intercourse. Medication was administered at most once within 24 h, twice per week, and 6 times within 4 weeks. Before and after treatment, the score of TCM symptoms, the score of premature ejaculation diagnostic tool (PEDT), intravaginal ejaculation latency time (IELT) and the serum sex hormone content (testosterone [T], luteinizing hormone [LH] and follicule stimulating hormone [FSH]) were observed and the clinical effect was evaluated in the three groups. RESULTS: After treatment, the scores for less duration of intercourse (<1 min), post-ejaculation fatigue, low spirit and decreased libido, and the total scores of TCM symptoms, as well as PEDT scores were reduced when compared with those before treatment in each group (P<0.01, P<0.05), and IELT was prolonged (P<0.01) in the three groups. The serum T content was increased when compared with that before treatment in the warm acupuncture group (P<0.05). After treatment, in comparison with the acupuncture group and the western medication group, the scores for post-ejaculation fatigue, soreness and weakness in the lumbar region and knee joints, decreased libido, insomnia, dream-disturbed sleep and frequent nocturnal enuresis, as well as the total score of TCM symptoms were lower (P<0.05, P<0.01) and the serum T content was increased (P<0.05) in the warm acupuncture group. When compared with the acupuncture group, PEDT scores were lower and IELT prolonged in the warm acupuncture group and the western medication group (P<0.05, P<0.01). The total effective rate was 82.7% (62/75) in the warm acupuncture group, higher than that of the acupuncture group (68.4%, 52/76) and the western medication group (64.9%, 48/74, P<0.05) respectively. CONCLUSION: Warm acupuncture with large-quantity moxibustion ameliorates the clinical symptoms and increases intravaginal ejaculation latency time and the levels of sex hormone in the patients with primary premature ejaculation (kidney deficiency and liver stagnation).

Microneedle Delivery Platform Integrated with Codelivery Nanoliposomes for Effective and Safe Androgenetic Alopecia Treatment.

Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, ß-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.

Metal exsolution from perovskite-based anodes in solid oxide fuel cells.

Solid oxide fuel cells (SOFCs) are highly efficient and environmentally friendly devices for converting fuel into electrical energy. In this regard, metal nanoparticles (NPs) loaded onto the anode oxide play a crucial role due to their exceptional catalytic activity. NPs synthesized through exsolution exhibit excellent dispersion and stability, garnering significant attention for comprehending the exsolution process mechanism and consequently improving synthesis effectiveness. This review presents recent advancements in the exsolution process, focusing on the influence of oxygen vacancies, A-site defects, lattice strain, and phase transformation on the variation of the octahedral crystal field in perovskites. Moreover, we offer insights into future research directions to further enhance our understanding of the mechanism and achieve significant exsolution of NPs on perovskites.

Local anesthetic delivery systems for the management of postoperative pain.

Postoperative pain (POP) is a major clinical challenge. Local anesthetics (LAs), including amide-type LAs, ester-type LAs, and other potential ion-channel blockers, are emerging as drugs for POP management because of their effectiveness and affordability. However, LAs typically exhibit short durations of action and prolonging the duration by increasing their dosage or concentration may increase the risk of motor block or systemic local anesthetic toxicity. In addition, techniques using LAs, such as intrathecal infusion, require professional operation and are prone to catheter displacement, dislodgement, infection, and nerve damage. With the development of materials science and nanotechnology, various LAs delivery systems have been developed to compensate for these disadvantages. Numerous delivery systems have been designed to continuously release a safe dose in a single administration to ensure minimal systemic toxicity and prolong pain relief. LAs delivery systems can also be designed to control the duration and intensity of analgesia according to changes in the external trigger conditions, achieve on-demand analgesia, and significantly improve pain relief and patient satisfaction. In this review, we summarize POP pathways, animal models and methods for POP testing, and highlight LAs delivery systems for POP management. STATEMENT OF SIGNIFICANCE: Postoperative pain (POP) is a major clinical challenge. Local anesthetics (LAs) are emerging as drugs for POP management because of their effectiveness and affordability. However, they exhibit short durations and toxicity. Various LAs delivery systems have been developed to compensate for these disadvantages. They have been designed to continuously release a safe dose in a single administration to ensure minimal toxicity and prolong pain relief. LAs delivery systems can also be designed to control the duration and intensity of analgesia to achieve on-demand analgesia, and significantly improve pain relief and patient satisfaction. In this paper, we summarize POP pathways, animal models, and methods for POP testing and highlight LAs delivery systems for POP management.

In Situ Encapsulation of SnS2/MoS2 Heterojunctions by Amphiphilic Graphene for High-Energy and Ultrastable Lithium-Ion Anodes.

Lithium-ion batteries with transition metal sulfides (TMSs) anodes promise a high capacity, abundant resources, and environmental friendliness, yet they suffer from fast degradation and low Coulombic efficiency. Here, a heterostructured bimetallic TMS anode is fabricated by in situ encapsulating SnS2/MoS2 nanoparticles within an amphiphilic hollow double-graphene sheet (DGS). The hierarchically porous DGS consists of inner hydrophilic graphene and outer hydrophobic graphene, which can accelerate electron/ion migration and strongly hold the integrity of alloy microparticles during expansion and/or shrinkage. Moreover, catalytic Mo converted from lithiated MoS2 can promote the reaction kinetics and suppress heterointerface passivation by forming a building-in-electric field, thereby enhancing the reversible conversion of Sn to SnS2. Consequently, the SnS2/MoS2/DGS anode with high gravimetric and high volumetric capacities achieves 200 cycles with a high initial Coulombic efficiency of >90%, as well as excellent low-temperature performance. When the commercial Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) cathode is paired with the prelithiated SnS2/MoS2/DGS anode, the full cells deliver high gravimetric and volumetric energy densities of 577 Wh kg-1 and 853 Wh L-1, respectively. This work highlights the significance of integrating spatial confinement and atomic heterointerface engineering to solve the shortcomings of conversion-/alloying typed TMS-based anodes to construct outstanding high-energy LIBs.

Multiple RNA Rapid In Situ Imaging Based on Cas9 Code Key System.

Existing RNA in situ imaging strategies mostly utilize parallel repetitive nucleic acid self-assembly to achieve multiple analysis, with limitations of complicated systems and cumbersome steps. Here, a Cas9 code key system with key probe (KP) encoder and CRISPR/Cas9 signal exporter is developed. This system triggers T-protospacer adjacent motif (T-PAM structural transitions of multiple KP encoders to form coding products with uniform single-guide RNA (sgRNA) target sequences as tandem nodes. Only single sgRNA/Cas9 complex is required to cleave multiple coding products, enabling efficient "many-to-one" tandem signaling, and non-collateral cleavage activity-dependent automatic signaling output through active introduction of mismatched bases. Compared with conventional parallel multiple signaling analysis model, the proposed system greatly simplifies reaction process and enhances detection efficiency. Further, a rapid multiple RNA in situ imaging system is developed by combining the Cas9 code key system with a T-strand displacement amplification (T-SDA) signal amplifier. The constructed system is applied to tumor cells and clinicopathology slices, generating clear multi-mRNA imaging profiles in less than an hour with just one step. Therefore, this work provides reliable technical support for clinical tumor typing and molecular mechanism investigation.

Inflammation and Late-Life Depression: Unraveling the Complex Relationship and Potential Therapeutic Strategies.

The origins of late-life depression are multifaceted and remain challenging to fully understand. While the traditional monoamine neurotransmitter hypothesis provides some insights, it falls short in explaining the disease's onset and progression, leaving treatments often less than optimal. There is an emergent need to uncover new underlying mechanisms. Among these, the "inflammation hypothesis" has been gaining traction in scientific discussions regarding late-life depression. There is compelling evidence linking inflammation processes to the emergence of this form of depression. This review delves into the nuanced relationship between inflammation and late-life depression, emphasizing the pivotal role and implications of inflammation in its pathogenesis. Changes in Ca2+ homeostasis, cytokine levels, brain-derived neurotrophic factor (BDNF), white cell ratios, and the involvement of the NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome have all been suggested as potential biomarkers that tie inflammation to late-life depression. Furthermore, factors such as aging-induced DNA damage, oxidative stress, mitochondrial impairments, disruptions in the hypothalamic-pituitary-adrenal axis, activated microglia and associated neuroinflammation, as well as the gut-brain axis dynamics, could serve as bridges between inflammation and depression. Deepening our understanding of these connections could usher in innovative anti-inflammatory treatments and strategies for late- life depression.