Logotherapy-Based Interventions for Chinese Family Caregivers of Older Adults with Dementia Through Online Groups: A Mixed-Methods Study.

Chinese family caregivers of people with dementia (PWD) can suffer from physical and psychological burden. This study aimed to examine the effects of logotherapy-based interventions on Chinese family caregivers of older adults with dementia to decrease caregiver burden. This mixed-methods study used a pre-experimental design with pre-posttests and semi-structured interviews. A purposive sample of 13 family caregivers from a suburban district in Shanghai was enrolled with (1) caregiver burden and (2) access and capability to use smart devices. Participants received eight online group logotherapy sessions with a focus on hope and meaning construction. Participants completed the Zarit Burden Interview, a 22-item measure of caregiver burden, before and after the intervention, and a 30-min semi-structured interview post-intervention. From the quantitative data, dementia caregivers reported severe caregiving burdens at the baseline (M = 54.77, SD = 9.33). Caregiver burden significantly decreased after the logotherapy-based intervention (M = 52.15, SD = 8.80, p < .001). Two themes pertaining to participants' experiences in intervention emerged from the qualitative data: (1) improved attitudes toward suffering, and (2) enhanced sense of meaning in life and hope. The cultural relevance of logotherapy to Chinese familism and Confucianism may further enhance its feasibility in the Chinese context.

SON is an essential m6A target for hematopoietic stem cell fate.

Stem cells regulate their self-renewal and differentiation fate outcomes through both symmetric and asymmetric divisions. m6A RNA methylation controls symmetric commitment and inflammation of hematopoietic stem cells (HSCs) through unknown mechanisms. Here, we demonstrate that the nuclear speckle protein SON is an essential m6A target required for murine HSC self-renewal, symmetric commitment, and inflammation control. Global profiling of m6A identified that m6A mRNA methylation of Son increases during HSC commitment. Upon m6A depletion, Son mRNA increases, but its protein is depleted. Reintroduction of SON rescues defects in HSC symmetric commitment divisions and engraftment. Conversely, Son deletion results in a loss of HSC fitness, while overexpression of SON improves mouse and human HSC engraftment potential by increasing quiescence. Mechanistically, we found that SON rescues MYC and suppresses the METTL3-HSC inflammatory gene expression program, including CCL5, through transcriptional regulation. Thus, our findings define a m6A-SON-CCL5 axis that controls inflammation and HSC fate.

The Identity of Nickel Peroxide as a Nickel Superoxyhydroxide for Enhanced Electrocatalysis.

Nickel peroxides are a class of stoichiometric oxidants that can selectively oxidize various organic compounds, but their molecular level structure remained elusive until now. Herein, we utilized structural prediction using the Stochastic Surface Walking method based on a neural network potential energy surface and advanced characterization using the as-synthesized nickel peroxide to unravel its chemical identity as the bridging superoxide containing nickel hydroxide, or nickel superoxyhydroxide. Superoxide incorporation tunes the local chemical environment of nickel and oxygen beyond the conventional Bode plot, offering a 6.4-fold increase in the electrocatalytic activity of urea oxidation. A volcanic dependence of the activity on the oxygen equivalents leads to the proposed active site of the Ni(OO)(OH)Ni five-membered ring. This work not only unveils the possible structures of nickel peroxides but also emphasizes the significance of tailoring the oxygen environment for advanced catalysis.

Simvastatin nanocrystals-based dissolving microneedles for wound healing.

Currently, one of the main problems encountered in wound healing therapy is related to inefficient drug delivery. However, dissolving microneedles (DMNs) can be administered percutaneously to effectively deliver a drug to a deep wound area. Simvastatin (SIM) can promote wound healing, albeit its insolubility in water limits its application. Here, we designed a DMNs (SIM-NC@DMNs) drug delivery system loaded with SIM nanocrystals (SIM-NC) and evaluated its efficacy in wound healing. Based on our observations, the dissolution performance of insoluble SIM is significantly improved after the preparation of SIM-NC. For example, the saturation solubility of SIM-NC in deionized water and PBS increased by 150.57 times and 320.14 times, respectively. After the SIM-NC@DMNs are deeply inserted into the wound, the needle portion, which is composed of hyaluronic acid (HA), dissolves rapidly, and the SIM-NC loaded on the needle portion is efficiently released into the deep wound area for optimal therapeutic efficacy. The combination of NC and DMNs makes this system further effective for wound healing. Our cumulative work suggests that the newly developed SIM-NC@DMNs possess great potential in accelerating wound healing. By day 12 after treatment, the residual wound area in the Control group was 21.34 %, while the residual wound area in the SIM-NC@DMNs group was only 2.36 %. This result as well as provides certain evidence of its efficacy for wound healing therapy. The SIM-NC@DMNs drug delivery system may become an efficient treatment modality that promotes wound healing, with a promising potential in the field of wound healing research.

Regulating the Innocuity of Urea Electro-Oxidation via Cation-mediated Adsorption.

Urea electrolysis is an emerging technology that bridges efficient wastewater treatment and hydrogen production with lower electricity costs. However, conventional Ni-based catalysts could easily overoxidize urea into the secondary contaminant NOx - , and enhancing the innocuity of urea electrolysis remains a grand challenge to be achieved. Herein, we tailored the electrode-electrolyte interface of an unconventional cation effect on the anodic oxidation of urea to regulate its activity and selectivity. Smaller cations of Li+ were discovered to increase the Faradaic efficiency (FE) of the innocuous N2 product from the standard value of ~15 % to 45 %, while decreasing the FEs of the over-oxidized NOx - product from ~80 % to 46 %, pointing to a more sustainable process. The kinetic and computational analysis revealed the dominant residence of cations on the outer Helmholtz layer, which forms the interactions with the surface adsorbates. The Li+ hydration shells and rigid hydrogen bonding network interact strongly with the adsorbed urea to decrease its adsorption energy and subjection to C-N cleavage, thereby directing it toward the N2 pathway. This work emphasizes the tuning of the interactions within the electrode-electrolyte interface for enhancing the efficiency and sustainability of electrocatalytic processes.

TP53 Exon 5 Mutation Indicates Poor Progression-Free Survival for Patients with Stage IV NSCLC.

BACKGROUND: Genetic mutations are quite common in non-small cell lung cancer (NSCLC), however, their prognostic value remains controversial. METHODS: This study explored the mutational landscape of tumor samples from patients with advanced NSCLC by next-generation sequencing (NGS). A total of 101 NSCLC patients in stage III or IV receiving first-line treatment were included. RESULTS: TP53 mutation was the most frequent genetic alteration in NSCLC tumors (68%), followed by EGFR (49%), CDKN2A (12%), LRP1B (9%), and FAT3 (9%) mutations. Among 85 patients with stage IV NSCLC, first-line targeted therapy remarkably prolonged progression-free survival (PFS) of patients compared with first-line chemotherapy (p = 0.0028). Among 65 patients with stage IV NSCLC whose tumors harbored EGFR, ALK, ROS, or BRAF mutations, first-line targeted therapy substantially prolonged the PFS of patients (p = 0.0027). In patients with TP53 mutations who received first-line targeted therapy or chemotherapy, missense mutation was the most common mutation type (36/78), and exon 5 represented the most common mutated site (16/78). CONCLUSIONS: TP53 mutation in exon 5 could independently predict poor PFS of patients with stage IV NSCLC after the first- line treatment. Moreover, mutations in TP53 exon 5 and LRP1B were associated with shorter PFS of such patients whether after first-line chemotherapy or targeted therapy, respectively. Thus, these patients should be given immunotherapy or immunochemotherapy.

Arabinose- and xylose-modified analogs of 2',3'-cGAMP act as STING agonists.

Stimulator of interferon genes (STING) agonists are promising candidates for vaccine adjuvants and antitumor immune stimulants. The most potent natural agonist of STING, 2',3'-cyclic GMP-AMP (2',3'-cGAMP), is subject to nuclease-mediated inherent metabolic instability, thereby placing limits on its clinical efficacy. Here, we report on a new class of chemically synthesized sugar-modified analogs of 2',3'-cGAMP containing arabinose and xylose sugar derivatives that bind mouse and human STING alleles with high affinity. The co-crystal structures demonstrate that such analogs act as 2',3'-cGAMP mimetics that induce the "closed" conformation of human STING. These analogs show significant resistance to hydrolysis mediated by ENPP1 and increased stability in human serum, while retaining similar potency as 2',3'-cGAMP at inducing IFN-ß secretion from human THP1 cells. The arabinose- and xylose-modified 2',3'-cGAMP analogs open a new strategy for overcoming the inherent nuclease-mediated vulnerability of natural ribose cyclic nucleotides, with the additional benefit of high translational potential as cancer therapeutics and vaccine adjuvants.

Modular Functionalization of Metal-Organic Frameworks for Nitrogen Recovery from Fresh Urine.

Nitrogen recovery from wastewater represents a sustainable route to recycle reactive nitrogen (Nr). It can reduce the demand of producing Nr from the energy-extensive Haber-Bosch process and lower the risk of causing eutrophication simultaneously. In this aspect, source-separated fresh urine is an ideal source for nitrogen recovery given its ubiquity and high nitrogen contents. However, current techniques for nitrogen recovery from fresh urine require high energy input and are of low efficiencies because the recovery target, urea, is a challenge to separate. In this work, we developed a novel fresh urine nitrogen recovery treatment process based on modular functionalized metal-organic frameworks (MOFs). Specifically, we employed three distinct modification methods to MOF-808 and developed robust functional materials for urea hydrolysis, ammonium adsorption, and ammonia monitoring. By integrating these functional materials into our newly developed nitrogen recovery treatment process, we achieved an average of 75 % total nitrogen reduction and 45 % nitrogen recovery with a 30-minute treatment of synthetic fresh urine. The nitrogen recovery process developed in this work can serve as a sustainable and efficient nutrient management that is suitable for decentralized wastewater treatment. This work also provides a new perspective of implementing versatile advanced materials for water and wastewater treatment.

Coordination-Promoted Bio-Catechol Electro-Reforming toward Sustainable Polymer Production.

Sustainable polymer production is essential for a carbon-neutral society. cis,cis-Muconic acid is attracting growing interest as a biomass-derived platform molecule with direct access to adipic acid and terephthalic acid, prominent monomers of commercial polymers. Here, a sustainable route of electro-reforming biorenewable catechol to cis,cis-muconic acid with concurrent H2 production has been proposed. By using a CuO foam electrode, a high cis,cis-muconate yield of 90% and a high faradaic efficiency of 87% can be achieved under ambient conditions without external oxidant. Zn2+ coordination with the catechol is central to the yield and selectivity. In a combinatory analysis via steady-state electrochemical kinetics, in situ spectroscopy, and theoretical calculation, we revealed that the reaction ensemble of catechol electrooxidation involves three major processes of polymerization, ring cleavage, and depolymerization, in which Zn2+ coordination is highly effective in delaying polymerization and promoting ring cleavage toward cis,cis-muconate. The catecholate coordinated to the Zn2+ cations reallocated its electron density with partial structural deformation to accelerate the electron transfer and facilitate the OH- nucleophilic attack. A practical two-electrode system was eventually demonstrated to efficiently and stably electro-reform catechol into isolable cis,cis-muconic acid and hydrogen, providing solutions for polymer sustainability via utilizing alternative biomass resources and electrified processes.

Kerstersia gyiorum isolated for the first time from two patients with neurodegenerative disease: report of two unusual cases and a review of the literature.

With the development of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal RNA (rRNA) gene sequencing, increasing numbers of new microorganisms are being discovered. In this report, Kerstersia gyiorum was isolated for the first time from the sputum of two elderly patients with neurodegenerative disease, and integrated traditional Chinese and Western medicine was used for treatment. The bacteria's growth characteristics, biochemical reaction characteristics, sensitivity to antibiotics, and the patients' treatment are described, with a review of previous reports.

Bartholin's gland cyst caused by Sneathia amnii: a case report.

BACKGROUND: Sneathia amnii is a conditional pathogen of the female genital tract that is involved in bacterial vaginosis and poor reproductive and perinatal outcomes. Few studies have reported subcutaneous cysts following invasive infection caused by S amnii. CASE PRESENTATION: Here we report the case of a 27-year-old woman who presented with Bartholin's gland cyst due to S amnii infection, and was successfully treated with surgical neostomy and antibiotic agents. The isolate was gram-negative, bacillary, anaerobic, and was identified by polymerase chain reaction (PCR) amplification of the 16 S rRNA. CONCLUSIONS: S amni is an important but underappreciated pathogen that needs further investigation. This report describes the microbial and pathogenic characteristics of S amnii and is expected to provide a valuable reference in obstetric and gynecologic clinical practice.

RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells.

Tissue homeostasis is maintained after stress by engaging and activating the hematopoietic stem and progenitor compartments in the blood. Hematopoietic stem cells (HSCs) are essential for long-term repopulation after secondary transplantation. Here, using a conditional knockout mouse model, we revealed that the RNA-binding protein SYNCRIP is required for maintenance of blood homeostasis especially after regenerative stress due to defects in HSCs and progenitors. Mechanistically, we find that SYNCRIP loss results in a failure to maintain proteome homeostasis that is essential for HSC maintenance. SYNCRIP depletion results in increased protein synthesis, a dysregulated epichaperome, an accumulation of misfolded proteins and induces endoplasmic reticulum stress. Additionally, we find that SYNCRIP is required for translation of CDC42 RHO-GTPase, and loss of SYNCRIP results in defects in polarity, asymmetric segregation, and dilution of unfolded proteins. Forced expression of CDC42 recovers polarity and in vitro replating activities of HSCs. Taken together, we uncovered a post-transcriptional regulatory program that safeguards HSC self-renewal capacity and blood homeostasis.

Synthesis of α-aryl sulfides by deaminative coupling of α-amino compounds with thiophenols.

By the deaminative coupling reaction of α-aminoesters and α-aminoacetonitriles with thiols, a new strategy for the synthesis of α-thioaryl esters and nitriles is described, representing an example of converting C(sp3)-N into C(sp3)-S bonds. The substrates form diazo compounds in situ in the presence of NaNO2, and then a transition-metal-free S-H bond insertion reaction occurs with thiophenol derivatives. The method is simple in operation and post-treatment and has good universality. The corresponding thioethers were obtained in moderate to good (up to 90%) yields under mild conditions.

Coordinated Immobilization and Rapid Conversion of Polysulfide Enabled by a Hollow Metal Oxide/Sulfide/Nitrogen-Doped Carbon Heterostructure for Long-Cycle-Life Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) are recognized as the prospective candidate in next-generation energy storage devices due to their gratifying theoretical energy density. Nonetheless, they still face the challenges of the practical application including low utilization of sulfur and poor cycling life derived from shuttle effect of lithium polysulfides (LiPSs). Herein, a hollow polyhedron with heterogeneous CoO/Co9 S8 /nitrogen-doped carbon (CoO/Co9 S8 /NC) is obtained through employing zeolitic imidazolate framework as precursor. The heterogeneous CoO/Co9 S8 /NC balances the redox kinetics of Co9 S8 with chemical adsorption of CoO toward LiPSs, effectively inhibiting the shuttle of LiPSs. The mechanisms are verified by both experiment and density functional theory calculation. Meanwhile, the hollow structure acts as a sulfur storage chamber, which mitigates the volumetric expansion of sulfur and maximizes the utilization of sulfur. Benefiting from the above advantages, lithium-sulfur battery with S-CoO/Co9 S8 /NC achieves a high initial discharge capacity (1470 mAh g-1 ) at 0.1 C and long cycle life (ultralow capacity attenuation of 0.033% per cycle after 1000 cycles at 1 C). Even under high sulfur loading of 3.0 mg cm-2 , lithium-sulfur battery still shows the satisfactory electrochemical performance. This work may provide an idea to elevate the electrochemical performance of LSBs by constructing a hollow metal oxide/sulfide/nitrogen-doped carbon heterogeneous structure.

5-aminolevulinic acid-loaded dissolving microneedle array for photodynamic therapy of rheumatoid arthritis on rats.

Photodynamic therapy (PDT) is a noninvasive technique that can be used to treat rheumatoid arthritis (RA) by irradiating photosensitizers with specific wavelengths of light to generate reactive oxygen species (ROS), thus leading to targeted cell necrosis. However, efficient delivery of photosensitizers with low side effects is a key issue. We developed a 5-aminolevulinic acid-loaded dissolving microneedle array (5-ALA@DMNA) that can locally and efficiently deliver photosensitizers for RA treatment by PDT. 5-ALA@DMNA was fabricated through a two-step molding process, which was characterized. The effects of 5-ALA-mediated PDT on RA fibroblast-like synoviocytes (RA-FLs) were investigated via in vitro experiments. Adjuvant arthritis rat models were established to evaluate the therapeutic effect of 5-ALA@DMNA-mediated PDT on RA. The results showed that 5-ALA@DMNA could penetrate the skin barrier and efficiently deliver photosensitizers. 5-ALA-mediated PDT can significantly inhibit the migration ability and selectively induce apoptosis of RA-FLs. Moreover, 5-ALA-mediated PDT had a significant therapeutic effect on rats with adjuvant arthritis, which may be related to the upregulation of interleukin (IL)- 4 and IL-10 and downregulation of TNF-α, IL-6, and IL-17. Thus, 5-ALA@DMNA-mediated PDT may be a potential therapy for RA.

Ligand vacancy channels in pillared inorganic-organic hybrids for electrocatalytic organic oxidation with enzyme-like activities.

Simultaneously achieving abundant and well-defined active sites with high selectivity has been one of the ultimate goals for heterogeneous catalysis. Herein, we construct a class of Ni hydroxychloride-based inorganic-organic hybrid electrocatalysts with the inorganic Ni hydroxychloride chains pillared by the bidentate N-N ligands. The precise evacuation of N-N ligands under ultrahigh-vacuum forms ligand vacancies while partially retaining some ligands as structural pillars. The high density of ligand vacancies forms the active vacancy channel with abundant and highly-accessible undercoordinated Ni sites, exhibiting 5-25 fold and 20-400 fold activity enhancement compared to the hybrid pre-catalyst and standard ß-Ni(OH)2 for the electrochemical oxidation of 25 different organic substrates, respectively. The tunable N-N ligand can also tailor the sizes of the vacancy channels to significantly impact the substrate configuration leading to unprecedented substrate-dependent reactivities on hydroxide/oxide catalysts. This approach bridges heterogenous and homogeneous catalysis for creating efficient and functional catalysis with enzyme-like properties.

Ligand Hybridization for Electro-reforming Waste Glycerol into Isolable Oxalate and Hydrogen.

The electro-reforming of glycerol is an emerging technology of simultaneous hydrogen production and biomass valorization. However, its complex reaction network and limited catalyst tunability restrict the precise steering toward high selectivity. Herein, we incorporated the chelating phenanthrolines into the bulk nickel hydroxide and tuned the electronic properties by installing functional groups, yielding tunable selectivity toward formate (max 92.7 %) and oxalate (max 45.3 %) with almost linear correlation with the Hammett parameters. Further combinatory study of intermediate analysis and various spectroscopic techniques revealed the electronic effect of tailoring the valence band that balances between C-C cleavage and oxidation through the key glycolaldehyde intermediate. A two-electrode electro-reforming setup using the 5-nitro-1,10-phenanthroline-nickel hydroxide catalyst was further established to convert crude glycerol into pure H2 and isolable sodium oxalate with high efficiency.

Formin protein DIAPH1 positively regulates PD-L1 expression and predicts the therapeutic response to anti-PD-1/PD-L1 immunotherapy.

Formins are evolutionarily conserved genes and profoundly affect cancer progression. This study aims to explore the expressions, prognostic values, and immunological correlations of Formins in cancer. Specific Formins were dysregulated and immuno-biologically correlated in breast cancer (BRCA). Formins showed different expression patterns, namely some were enriched in immune cells while some were enriched in tumor cells. Among all Formins, DIAPH1 was enriched in tumor cells and associated with an inflamed tumor microenvironment (TME). DIAPH1 functioned as an oncogene in BRCA and mediated TGF-ß1-induced epithelial-mesenchymal transformation (EMT) and PD-L1 expression. Moreover, DIAPH1 was overexpressed in most cancers and functioned as a novel pan-cancer immuno-marker, which could predict the response to anti-PD-1/PD-L1 immunotherapy. Overall, DIAPH1 functions as an oncogene and is immunologically correlated, which could be utilized as an alternative biomarker for predicting the immunotherapeutic response.

Safety and efficacy analysis of PD-1 inhibitors in combination with chemotherapy for advanced pancreatic cancer.

Objective: To investigate the safety and efficacy of anti-PD-1 antibodies in combination with chemotherapy in the treatment of advanced pancreatic cancer. Methods: The clinical data of 18 patients with advanced pancreatic cancer who received anti-PD-1 antibody combined with chemotherapy were retrospectively analyzed. Safety, objective response rate, disease control rate, progression-free survival and overall survival were analyzed. Results: One patient achieved a complete response, nine patients had a partial response, five patients had stable disease and three patients had progressive disease. Progression-free survival and overall survival were shown to be significantly prolonged in both PD-L1-positive and high microsatellite instability (MSI-H) patients. Conclusion: Anti-PD-1 antibodies in combination with chemotherapy are safe and effective in the treatment of advanced pancreatic cancer.

In recent years, encouraging results have been achieved with a new treatment for advanced cancer, immunotherapy. Immune checkpoint inhibitors are now being used as a more established form of immunotherapy. During immunotherapy, immune checkpoint inhibitors effectively dismantle the 'camouflage' of tumor cells, allowing immune cells to regain the ability to recognize and remember them, allowing the body's immune cells or drugs to kill tumor cells with precision. This study analyzed 18 patients with advanced pancreatic cancer, in whom immunotherapy in combination with chemotherapy achieved better results than conventional treatment with minimal side effects, making immunotherapy one of the most promising treatments for tumors.

Antibiotic Resistance, Molecular Characteristics and Risk Factors of Carbapenem-Resistant Klebsiella pneumoniae in Clinical Isolates.

Background: The global epidemic of carbapenem-resistant Klebsiella pneumonia (CRKP) has become a significant public health challenge. This study aimed to investigate the antibiotic resistance and molecular characteristics of CRKP and the clinical characteristics of infected patients. Methods: Sixty-two clinically isolated CRKP strains were collected for the first time from the First Affiliated Hospital of Zhejiang Chinese Medical University in Zhejiang Province. The carbapenemase gene, virulence-associated gene, capsular serotype gene and fenestra protein gene were detected by PCR. Univariate logistic regression and multivariate logistic regression analyses were performed to predict the risk factors for the prognosis of CRKP infection. Results: All CRKP isolates were resistant to meropenem, piperacillin-tazobactam, and ceftazidime (100%, 62/62), and all but one CRKP isolate was resistant to imipenem and cefepime (96.8%, 61/62). The rate of colistin resistance was the lowest (11.9%, 8/62). For CRKP in the ICU, the rates of resistance to various antibiotics were significantly higher than those in general ward patients. Fifty strains carried the carbapenemase gene bla KPC, and 3 strains carried both the bla KPC and bla NDM genes. The virulence genes uge, wabG, ycf, entB, ureA and fimH were detected in more than 90% of the 62 CRKP strains. Two strains had Ompk35, Ompk36 and Hcp gene deletions. The bla KPC, rmpA and rmpA2 genes had the highest positive rate in blood samples, and bla NDM had the highest positive rate in stool samples. Multivariate analysis showed that pulmonary disease affected the prognosis of CRKP infection. Conclusion: The prevalence and molecular characteristics of CRKP clinical isolates in Zhengjiang Province in China were described, and the antibiotic resistance rate was higher. Additionally, relevant genes of CRKP strains and clinical characteristics of patients are related to the progression and prognosis of CRKP infection.