hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis.

BACKGROUND: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear. Herein, we investigated the regularity of acinar cell pyroptosis during SAP and investigated whether the protective effect of hP-MSCs was associated with the inhibition of acinar cell pyroptosis. METHODS: A mouse model of SAP was established by the retrograde injection of sodium taurocholate (NaTC) solution in the pancreatic duct. For the hP-MSCs group, hP-MSCs were injected via the tail vein and were monitored in vivo. Transmission electron microscopy (TEM) was used to observe the pyroptosis-associated ultramorphology of acinar cells. Immunofluorescence and Western blotting were subsequently used to assess the localization and expression of pyroptosis-associated proteins in acinar cells. Systemic inflammation and local injury-associated parameters were evaluated. RESULTS: Acinar cell pyroptosis was observed during SAP, and the expression of pyroptosis-associated proteins initially increased, peaked at 24 h, and subsequently showed a decreasing trend. hP-MSCs effectively attenuated systemic inflammation and local injury in the SAP model mice. Importantly, hP-MSCs decreased the expression of pyroptosis-associated proteins and the activity of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in acinar cells. CONCLUSIONS: Our study demonstrates the regularity and important role of acinar cell pyroptosis during SAP. hP-MSCs attenuate inflammation and inhibit acinar cell pyroptosis via suppressing NLRP3 inflammasome activation, thereby exerting a protective effect against SAP.

Bright near-infrared emission from the Au39(SR)29 nanocluster.

The synthesis of atomically precise gold nanoclusters with high photoluminescence quantum yield (PLQY) in the near-infrared (NIR) region and understanding their photoluminescence mechanism are crucial for both fundamental science and practical applications. Herein, we report a highly luminescent, molecularly pure Au39(PET)29 (PET = 2-phenylethanethiolate) nanocluster with PLQY of 19% in the NIR range (915 nm). Steady state and time-resolved PL analyses, as well as temperature-dependent PL measurements reveal the emission nature of Au39(PET)29, which consists of prompt fluorescence (weak), thermally activated delayed fluorescence (TADF), and phosphorescence (predominant). Furthermore, strong dipole-dipole interaction in the solid-state (e.g., Au39(PET)29 nanoclusters embedded in a polystyrene thin-film) is found to narrow the energy gap between the S1 and T1 states, which results in faster intersystem crossing and reverse intersystem crossing; thus, the ratio of TADF to phosphorescence varies and the total PLQY is increased to 32%. This highly luminescent nanocluster holds promise in imaging, sensing and optoelectronic applications.

Three-atom-wide gold quantum rods with periodic elongation and strongly polarized excitons.

Atomically precise control over anisotropic nanoclusters constitutes a grand challenge in nanoscience. In this work, we report our success in achieving a periodic series of atomically precise gold quantum rods (abbrev. Au QRs) with unusual excitonic properties. These QRs possess hexagonal close-packed kernels with a constant three-atom diameter but increasing aspect ratios (ARs) from 6.3 to 18.7, all being protected by the same thiolate (SR) ligand. The kernels of the QRs are in a Au1-(Au3)n-Au1 configuration (where n is the number of Au3 layers) and follow a periodic elongation with a uniform Au18(SR)12 increment consisting of four Au3 layers. These Au QRs possess distinct HOMO-LUMO gaps (Eg = 0.6 to 1.3 eV) and exhibit strongly polarized excitonic transition along the longitudinal direction, resulting in very intense absorption in the near-infrared (800 to 1,700 nm). While excitons in gapped systems and plasmons in gapless systems are distinctly different types of excitations, the strongly polarized excitons in Au QRs surprisingly exhibit plasmon-like behaviors manifested in the shape-induced polarization, very intense absorption (~106 M-1 cm-1), and linear scaling relations with the AR, all of which resemble the behaviors of conventional metallic-state Au nanorods (i.e., gapless systems), but the QRs possess distinct gaps and very long excited-state lifetimes (10 to 2,122 ns), which hold promise in applications such as near-infrared solar energy utilization, hot carrier generation and transfer. The observation of plasmon-like behaviors from single-electron transitions in Au QRs elegantly bridges the distinct realms of single-electron and collective-electron excitations and may stimulate more research on excitonics and plasmonics.

Visible to NIR-II Photoluminescence of Atomically Precise Gold Nanoclusters.

Atomically precise gold nanoclusters (NCs) have emerged as a new class of precision materials and attracted wide interest in recent years. One of the unique properties of such nanoclusters pertains to their photoluminescence (PL), for it can widely span visible to near-infrared-I and -II wavelengths (NIR-I/II), and even beyond 1700 nm by manipulating the size, structure, and composition. The current research efforts focus on the structure-PL correlation and the development of strategies for raising the PL quantum yields, which is nontrivial when moving from the visible to the near-infrared wavelengths, especially in the NIR-II regions. This review summarizes the recent progress in the field, including i) the types of PL observed in gold NCs such as fluorescence, phosphorescence, and thermally activated delayed fluorescence, as well as dual emission; ii) some effective strategies that are devised to improve the PL quantum yield (QY) of gold NCs, such as heterometal doping, surface rigidification, and core phonon engineering, with double-digit QYs for the NIR PL on the horizons; and iii) the applications of luminescent gold NCs in bioimaging, photosensitization, and optoelectronics. Finally, the remaining challenges and opportunities for future research are highlighted.

A Stable Reverse Genetics System of Zika Virus Based on a Self-Splicing Group II Intron.

Zika virus (ZIKV) is a mosquito-borne flavivirus of the Flaviviridae family first isolated from a sentinel monkey in the Zika Forest, Uganda, in 1947. Since 2007, the virus has had a vast geographic expansion that extended to the Americas in 2015, leading to a series of large outbreaks. Although mainly transmitted by the bite of Aedes mosquitoes, human infection of ZIKV can also happen through unconventional routes such as sexual intercourse and, more importantly, vertical transmission. The genome of ZIKV is a single-stranded, positive-sense RNA molecule about 11 kb in length. The genome contains a single opening reading frame (ORF) flanked by highly structured 5' and 3' untranslated regions. To understand the mechanisms about ZIKV replication, transmission, and pathogenesis, reverse genetic tools are of great importance. In this chapter, a novel system is described for the generation and manipulation of a ZIKV infectious clone stabilized by a self-splicing group II intron, a mobile element with ribozyme activity. The intron can be spliced in vitro, and thus full-length vRNA can be prepared allowing virus genome manipulation required for further studies.

Prime editing-mediated correction of the CFTR W1282X mutation in iPSCs and derived airway epithelial cells.

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.

Tailoring Carbon Tails of Ligands on Au52(SR)32 Nanoclusters Enhances the Near-Infrared Photoluminescence Quantum Yield from 3.8 to 18.3.

One of the important factors that determine the photoluminescence (PL) properties of gold nanoclusters pertain to the surface. In this study, four Au52(SR)32 nanoclusters that feature a series of aromatic thiolate ligands (-SR) with different bulkiness at the para-position are synthesized and investigated. The near-infrared (NIR) photoluminescence (peaks at 900-940 nm) quantum yield (QY) is largely enhanced with a decrease in the ligand's para-bulkiness. Specifically, the Au52(SR)32 capped with the least bulky p-methylbenzenethiolate (p-MBT) exhibits the highest PLQY (18.3% at room temperature in non-degassed dichloromethane), while Au52 with the bulkiest tert-butylbenzenethiolate (TBBT) only gives 3.8%. The large enhancement of QY with fewer methyl groups on the ligands implies a nonradiative decay via the multiphonon process mediated by C-H bonds. Furthermore, single-crystal X-ray diffraction (SCXRD) comparison of Au52(p-MBT)32 and Au52(TBBT)32 reveals that fewer methyl groups at the para-position lead to a stronger interligand π···π stacking on the Au52 core, thus restricting ligand vibrations and rotations. The emission nature is identified to be phosphorescence and thermally activated delayed fluorescence (TADF) based on the PL lifetime, 3O2 quenching, and temperature-dependent PL and absorption studies. The 1O2 generation efficiencies for the four Au52(SR)32 NCs follow the same trend as the observed PL performance. Overall, the highly NIR-luminescent Au52(p-MBT)32 nanocluster and the revealed mechanisms are expected to find future applications.

Comparison of heterologous prime-boost immunization strategies with DNA and recombinant vaccinia virus co-expressing GP3 and GP5 of European type porcine reproductive and respiratory syndrome virus in pigs.

Vaccination is principally used to control and treat porcine reproductive and respiratory syndrome virus (PRRSV) infection. This study investigated immunogenicity and protective efficacy of heterologous prime-boost regimens in pigs, including recombinant DNA and vaccinia virus vectors coexpressing PRRSV European genotype (EU) isolate GP3 and GP5: group A, pVAX1-EU-GP3-GP5 prime and rddVTT-EU-GP3-GP5 boost; group B, rddVTT-EU-GP3-GP5 prime and pVAX1-EU-GP3-GP5 boost; group C, empty vector pVAX1; group D, E3L gene-deleted vaccinia virus E3L- VTT. Vaccine efficacy was tested in an EU-type PRRSV (Lelystad virus strain) challenge pig model based on evaluating PRRSV-specific antibody responses, neutralizing antibodies, cytokines, T lymphocyte proliferation, CD4+ and CD8+ T lymphocytes, clinical symptoms, viremia and tissue virus loads. Plasmid DNA was delivered as chitosan-DNA nanoparticles, and Quil A (Quillaja) was used to increase vaccine efficiency. All piglets were boosted 21 days post the initial inoculation (dpi) and then challenged 14 days later. At 14, 21, 28 and 35 dpi, groups A and B developed significantly higher PRRSV-specific antibody responses compared with control groups C and D. Two weeks after the boost, significant differences in neutralizing antibody and IFN-γ levels were observed between groups A, C, D and B. At 49 dpi, groups A and B had markedly increased peripheral blood CD3+CD4+ T cell levels. Following virus challenge, group A showed viremia, but organ virus loads were lower than those in other groups. Thus, a heterologous prime-boost vaccine regimen (rddVTT-EU-GP3-GP5 prime, pVAX1-EU-GP3-GP5 boost) can improve humoral- and cell-mediated immune responses to provide resistance to EU-type PRRSV infection in vivo.

Elucidating the Near-Infrared Photoluminescence Mechanism of Homometal and Doped M25(SR)18 Nanoclusters.

More than a decade of research on the photoluminescence (PL) of classic Au25(SR)18 and its doped nanoclusters (NCs) still leaves many fundamental questions unanswered due to the complex electron dynamics. Here, we revisit the homogold Au25 (ligands omitted hereafter) and doped NCs, as well as the Ag25 and doped ones, for a comparative study to disentangle the influencing factors and elucidate the PL mechanism. We find that the strong electron-vibration coupling in Au25 leads to weak PL in the near-infrared region (∼1000 nm, quantum yield QY = 1% in solution at room temperature). Heteroatom doping of Au25 with a single Cd or Hg atom strengthens the coupling of the exciton with staple vibrations but reduces the coupling with the core breathing and quadrupolar modes. The QYs of the three MAu24 NCs (M = Hg, Au, and Cd) follow a linear relation with their PL lifetimes, suggesting a mechanism of suppressed nonradiative decay in PL enhancement. In contrast, the weaker electron-vibration coupling in Ag25 leads to higher PL (QY = 3.5%), and single Au atom doping further leads to a 5× enhancement of the radiative rate and a suppression of nonradiative decay rate (i.e., twice the PL lifetime of Ag25) in AuAg24 (hence, QY 35%), but doping more Au atoms results in gold distribution to staple motifs and thus triggering of strong electron-vibration coupling as in the MAu24 NCs, hence, counteracting the radiative enhancement effect and giving rise to only 5% QY for AuxAg25-x (x = 3-10). The obtained insights will provide guidance for the design of metal NCs with high PL for lighting, sensing, and optoelectronic applications.

Efficient inverted CsPbI3 inorganic perovskite solar cells achieved by facile surface treatment with ethanolamine.

The all-inorganic CsPbI3 perovskite presents promising prospects due to its suitable band gap and nonvolatile nature, while serious nonradiative recombination and unmatched energy level alignment hinder its further developments. Here, a facile and effective surface treatment strategy is proposed to modify the CsPbI3 surface with ethanolamine, leading to significantly reduced defects, and ameliorated band alignment and morphology. Consequently, a champion power conversion efficiency of 18.41% with improved stability is achieved for the inverted CsPbI3 solar cells.

Clinical application of ultrasound-guided thoracic nerve block in the operation of benign breast tumors.

OBJECTIVE: To analyze the application of ultrasound-guided thoracic nerve block (TNB) in the operation of benign breast tumors. METHODS: A retrospective analysis was conducted on 69 patients who underwent resection of benign breast tumors (fibroma, segment) in the Maternity and Child Care Center of Qinhuangdao from January 2021 to June 2022. Among them, 33 patients who received TNB were assigned to an observation group, and 36 patients who received local infiltration anesthesia were assigned to a control group. The heart rate (HR) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) of patients were recorded before anesthesia (T0), at skin incision (T1), at 0.5 h after operation (T2) and before leaving the operating room (T3). We also recorded the operation indexes, comprising operation time, total propofol dosage administered during operation, anesthesia recovery time and extubation time. The visual analogue scale (VAS) score was evaluated at 0.5, 2, 4 and 6 h after the operation. The two groups were also compared in terms of the levels of immunoglobulin (Ig) A, IgG, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The postoperative adverse reactions in the two groups were statistically analyzed. RESULTS: Compared with the observation group, the control group experienced a longer operation time, anesthesia recovery time and extubation time and consumed more propofol (P < 0.001). At T0 and T1, the two groups were not notably different in SBP, DBP and HR (P > 0.05), but at T2 and T3, the control group showed higher SBP, DBP and HR than the observation group (P < 0.001). The control group exhibited notably higher VAS scores than the observation group (P < 0.001). Before operation, the differences in the levels of IgA, IgG, IL-6 and TNF-α were not significantly different between the two groups (P > 0.05), while after operation and at 24 h after operation, the control group showed higher levels of IgA, IgG, IL-6 and TNF-α in comparison to the observation group (P < 0.01). The incidences of adverse reactions were not significantly different between the two groups (P > 0.05). CONCLUSION: Ultrasound-guided TNB can substantially reduce both the operation time and the postoperative pain in patients with benign breast tumors, without increasing the incidence of adverse reactions.

Specialized cis-Acting RNA Elements Balance Genome Cyclization to Ensure Efficient Replication of Yellow Fever Virus.

Genome cyclization is essential for viral RNA (vRNA) replication of the vertebrate-infecting flaviviruses, and yet its regulatory mechanisms are not fully understood. Yellow fever virus (YFV) is a notorious pathogenic flavivirus. Here, we demonstrated that a group of cis-acting RNA elements in YFV balance genome cyclization to govern efficient vRNA replication. It was shown that the downstream of the 5'-cyclization sequence hairpin (DCS-HP) is conserved in the YFV clade and is important for efficient YFV propagation. By using two different replicon systems, we found that the function of the DCS-HP is determined primarily by its secondary structure and, to a lesser extent, by its base-pair composition. By combining in vitro RNA binding and chemical probing assays, we found that the DCS-HP orchestrates the balance of genome cyclization through two different mechanisms, as follows: the DCS-HP assists the correct folding of the 5' end in a linear vRNA to promote genome cyclization, and it also limits the overstabilization of the circular form through a potential crowding effect, which is influenced by the size and shape of the DCS-HP structure. We also provided evidence that an A-rich sequence downstream of the DCS-HP enhances vRNA replication and contributes to the regulation of genome cyclization. Interestingly, diversified regulatory mechanisms of genome cyclization, involving both the downstream of the 5'-cyclization sequence (CS) and the upstream of the 3'-CS elements, were identified among different subgroups of the mosquito-borne flaviviruses. In summary, our work highlighted how YFV precisely controls the balance of genome cyclization to ensure viral replication. IMPORTANCE Yellow fever virus (YFV), the prototype of the Flavivirus genus, can cause devastating yellow fever disease. Although it is preventable by vaccination, there are still tens of thousands of yellow fever cases per year, and no approved antiviral medicine is available. However, the understandings about the regulatory mechanisms of YFV replication are obscure. In this study, by a combination of bioinformatics, reverse genetics, and biochemical approaches, it was shown that the downstream of the 5'-cyclization sequence hairpin (DCS-HP) promotes efficient YFV replication by modulating the conformational balance of viral RNA. Interestingly, we found specialized combinations for the downstream of the 5'-cyclization sequence (CS) and upstream of the 3'-CS elements in different groups of the mosquito-borne flaviviruses. Moreover, possible evolutionary relationships among the various downstream of the 5'-CS elements were implied. This work highlighted the complexity of RNA-based regulatory mechanisms in the flaviviruses and will facilitate the design of RNA structure-targeted antiviral therapies.

Size Effects of Atomically Precise Gold Nanoclusters in Catalysis.

The emergence of ligand-protected, atomically precise gold nanoclusters (NCs) in recent years has attracted broad interest in catalysis due to their well-defined atomic structures and intriguing properties. Especially, the precise formulas of NCs provide an opportunity to study the size effects at the atomic level without complications by the polydispersity in conventional nanoparticles that obscures the relationship between the size/structure and properties. Herein, we summarize the catalytic size effects of atomically precise, thioate-protected gold NCs in the range of tens to hundreds of metal atoms. The catalytic reactions include electrochemical catalysis, photocatalysis, and thermocatalysis. With the precise sizes and structures, the fundamentals underlying the size effects are analyzed, such as the surface area, electronic properties, and active sites. In the catalytic reactions, one or more factors may exert catalytic effects simultaneously, hence leading to different catalytic-activity trends with the size change of NCs. The summary of literature work disentangles the underlying fundamental mechanisms and provides insights into the size effects. Future studies will lead to further understanding of the size effects and shed light on the catalytic active sites and ultimately promote catalyst design at the atomic level.

Gut microbiota-derived melatonin from Puerariae Lobatae Radix-resistant starch supplementation attenuates ischemic stroke injury via a positive microbial co-occurrence pattern.

Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic; however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter, Bacteroidales_S24-7_group, Prevotella_9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke.

Effect of Cu addition to AISI 8630 steel on the resistance to microbial corrosion.

Low-alloy, high-strength structural steel AISI 8630 is exposed to severe microbiologically influenced corrosion (MIC) in its application environment. To address this issue, we independently designed and developed an AISI 8630 steel containing 0.4 wt% Cu (Cu-AISI 8630) to exploit the Cu antimicrobial effect. The corrosion behavior of two steels in the presence of marine Pseudomonas aeruginosa biofilm was explored by analyzing weight loss, electrochemical tests, SEM images, corrosion pit dimensions, and corrosion products. The electrochemical test results showed an increase in Rp and a significant positive shift in Ecorr for Cu-AISI 8630 steel compared to AISI 8630 steel during the immersion cycles. A comparison of the pit morphology of AISI 8630 steel and Cu-AISI 8630 steel after 14 days showed that the maximum MIC pit depth was significantly reduced in the latter compared to the former (3.65 µm vs 9.47 µm). The XPS results showed that protective Cu2O and CuO layers were formed on the surface of Cu-AISI 8630 steel. The experimental results show that Cu improves the MIC resistance of Pseudomonas aeruginosa biofilms significantly.

Oral Supplementation with Maca Improves Social Recognition Deficits in the Valproic Acid Animal Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a congenital, lifelong neurodevelopmental disorder whose main symptom is impaired social communication and interaction. However, no drug can treat social deficits in patients with ASD, and treatments to alleviate social behavioral deficits are sorely needed. Here, we examined the effect of oral supplementation of maca (Lepidium meyenii) on social deficits of in utero-exposed valproic acid (VPA) mice, widely used as an ASD model. Although maca is widely consumed as a fertility enhancer and aphrodisiac, it possesses multiple beneficial activities. Additionally, it benefits learning and memory in experimental animal models. Therefore, the effect of maca supplementation on the social behavioral deficit of VPA mice was assessed using a social interaction test, a three-stage open field test, and a five-trial social memory test. The oral supplementation of maca attenuated social interaction behavior deficit and social memory impairment. The number of c-Fos-positive cells and the percentage of c-Fos-positive oxytocin neurons increased in supraoptic and paraventricular neurons of maca-treated VPA mice. These results reveal for the first time that maca is beneficial to social memory and that it restores social recognition impairments by augmenting the oxytocinergic neuronal pathways, which play an essential role in diverse social behaviors.

Photoluminescence of the Au38(SR)26 nanocluster comprises three radiative processes.

Photoluminescence of ultrasmall, atomically precise gold nanoclusters constitutes an area of significant interest in recent years for both fundamental research and biological applications. However, the exploration of near-infrared photoluminescence of gold nanoclusters is still in its infancy due to the limitations of synthetic methods and characterization techniques. Herein, the photoluminescence properties of an Au38(PET)26 (PET = 2-phenylethanethiolate) nanocluster are investigated in detail. The Au38(PET)26 exhibits an emission peak at 865 nm, which is revealed to be a mix of fluorescence, thermally activated delayed fluorescence, and phosphorescence via the combined analyses of time-resolved and temperature-dependent photoluminescence measurements. The quantum yield of Au38(PET)26 is determined to be 1.8% at room temperature under ambient conditions, which increases to above 90% by suppressing the non-radiative relaxation pathway at a cryogenic temperature (80 K). Overall, the results of this work discover the coexistence of three radiative processes in thiolate-protected Au nanoclusters and will pave the way for understanding the intriguing photoluminescence properties of gold nanoclusters in future studies.

Heterogeneity of clinical symptoms and therapeutic strategies for different subtypes of adenomyosis: An initial single-center study in China.

OBJECTIVE: To investigate the relationship between the magnetic resonance imaging (MRI) classification of different clinical symptoms and corresponding therapeutic efficacy in adenomyosis patients. METHODS: From January 2015 to October 2020, a total of 468 patients diagnosed with adenomyosis through MRI examination at Peking University Third Hospital were included in this retrospective cohort study. Totals of 184 (39.3%), 208 (44.4%), 17 (3.6%), and 59 (12.6%) patients were categorized into Subtypes I (intrinsic), II (extrinsic), III (intramural), and IV (penetrating), respectively. Clinical information such as age, dysmenorrhea, menorrhagia, infertility, assisted reproduction, and drug treatment and its efficacy were analyzed. By comparing the clinical information of different adenomyosis subtypes, we intend to provide better fertility guidance and find better treatment strategies for these patients. RESULTS: The proportion of dysmenorrhea increased in intrinsic, extrinsic, intramural, and penetrating subtypes (74.5% vs 82.7% vs 94.1% vs 94.9%, respectively, P = 0.002). The proportion of menorrhagia in the intrinsic subtype (53.3%) was significantly higher than that in the extrinsic (28.4%) and intramural (29.4%) subtypes (P < 0.001). The effective rate of progesterone in the intrinsic subtype was significantly lower than that in the extrinsic subtype (52.0% vs 86.5%, P < 0.001). The infertility rates of adenomyosis patients with different subtypes were relatively high (17.6%-41.3%), and that of the extrinsic subtype was the highest among all the subtype groups (41.3%, P < 0.001). CONCLUSIONS: Significant differences in age, dysmenorrhea, menorrhagia, and infertility were found among patients with different subtypes of adenomyosis. A novel classification of adenomyosis was proposed to provide a theoretical basis for the treatment of adenomyosis patients with infertility.

Fibroblast ferroptosis is involved in periodontitis-induced tissue damage and bone loss.

Periodontitis causes inflammatory destructions of tooth-supporting tissue and constitutes a significant burden on public health. Failing to reserve the tissue damage and bone loss by any of the currently available therapies has left periodontitis uncurable thus far. Understanding the molecular mechanism in the inflammatory process is crucial to elucidating the pathogenesis and enlightening new therapeutic strategies for periodontitis. This study was to investigate whether and how ferroptosis, a newly-discovered form of cell death, was involved in the pathogenesis of periodontitis. Healthy and periodontitis human gingiva samples were collected and ligature-induced periodontitis murine models were constructed to investigate the role of ferroptosis in periodontitis. Single-cell RNA sequencing data was analyzed to identify the cell type that underwent ferroptosis. The susceptibility of human gingival fibroblasts to ferroptosis was investigated by in vitro cell cultures. We found that gingival fibroblasts undergo ferroptosis in periodontitis, and that periodontitis-induced tissue damage and bone loss were alleviated by inhibition of ferroptosis. Periodontitis-induced pro-inflammatory immune responses was featured by profound elevation of fibroblast-derived Interleukin-6, which was attenuated by ferroptosis inhibition. These results indicated fibroblast ferroptosis as a new clue to unveiling the cellular and molecular basis for periodontitis-induced tissue damage. Involvement of ferroptosis/Interleukin-6 signaling in the pathogenic process suggested a potential target for immunopharmacological approaches to curing periodontitis.

Size-Dependent Electrocatalytic Water Oxidation Activity for a Series of Atomically Precise Nickel-Thiolate Clusters.

The development of renewable energy technologies is critical for reducing global carbon emissions. Water splitting offers a promising renewable energy mechanism by converting water into H2 and O2 gas, which can directly power fuel cells or be utilized as chemical feedstocks. To increase the efficiency of water splitting, catalysts must be developed for the water reduction and water oxidation half-reactions. To promote rational catalyst design, atomically precise metal clusters (APMCs) with earth-abundant metals provide a framework for developing both structure-activity relationships and cost-effective catalysts. Previous reports on the water oxidation activity of nickel-thiolate clusters [Nin(SR)2n] have not developed a systematic description of a possible size-activity relationship. Utilizing recent advancements in preparative chromatography for isolating APMCs, we have synthesized a series of Nin(SR)2n (n = 4, 5, or 6) clusters as electrocatalysts for the oxygen evolution reaction. We discovered a clear size-activity and size-stability trend, with intrinsic activity and stability increasing with cluster size. Using density functional theory, we found that intrinsic activity is inversely correlated to intermediate binding energy, and by extension the oxidation potential of each cluster. Our work demonstrates the ability of APMCs to uncover previously unknown structure-activity relationships that can guide future catalyst design.