Diagnostic performance of rapid antigen tests (RAT) for COVID-19 and factors associated with RAT-negative results among RT-PCR-positive individuals during Omicron BA.2, BA.5 and XBB.1 predominance.

BACKGROUND: While numerous studies have evaluated the real-world performance of rapid antigen tests (RATs), data on the effect of Omicron sublineages such as XBB and reinfections on RAT performance is limited. We assessed the performance of RATs and factors associated with RAT-negative results among individuals who tested SARS-CoV-2-positive by reverse transcription-polymerase chain reaction (RT-PCR). METHODS: We conducted a retrospective study among Singapore residents who underwent testing for SARS-CoV-2 with RAT (Acon Flowflex or SD Biosensor) and RT-PCR in the same clinical encounter between 9 May 2022 and 21 November 2022. RT-PCR served as a reference standard for RAT performance. Logistic regression was used to estimate the odds ratios (OR) of factors associated with negative RAT results among RT-PCR-positive cases. RESULTS: Of 8,620 clinical encounters analysed, 3,519 (40.8%) were SARS-CoV-2-positive on RT-PCR. Overall sensitivity and specificity of RAT was 84.6% (95% CI 83.3-85.7%) and 99.4% (95% CI 99.1-99.6%) respectively. Acon Flowflex consistently achieved higher sensitivity and specificity than SD Biosensor test kit. Among RT-PCR-positive cases, individuals who had a previous documented SARS-CoV-2 infection, coinfection with another respiratory pathogen or tested ≥ 6 days from symptom onset had higher odds of testing RAT-negative, but the associations were attenuated after adjustment for cycle threshold values (proxy for viral load). There was no significant difference in RAT performance between Omicron sublineages BA.2, BA.5 and XBB.1. CONCLUSION: Diagnostic performance of RAT was not affected by changes in predominant circulating Omicron sublineages. However, reinfection cases may be under ascertained by RAT. In individuals with a previous SARS-CoV-2 infection episode or symptom onset ≥ 6 days prior to testing, a confirmatory RT-PCR may be considered if there is high clinical suspicion.

[Establishment of a rapid detection method of colloidal gold immunochromatographic competition assay for organophosphorus pesticides].

Objective To establish a colloidal gold immunochromatography and develop the corresponding test strip for detecting organophosphorus compounds including omethoate, phoxim, dipterex, and parathion in fruits, vegetables and drinking water. Methods Artificial antigen molecules of organophosphorus compounds were synthesized using N-hydroxysuccinimide esters. Acetylcholinesterase antigen was prepared and purified, and the serum containing the corresponding antibody was prepared, purified, and labeled. The working parameters of the test strip were optimized, and the performance evaluation of it was conducted. Results The titer of the antisera ranged from 1:32 to 1:64, with a protein content of approximately 2 mg/mL. The purified polyclonal antibodies displayed target bands at relative molecular masses (Mr) of 25 000 and 55 000, indicating satisfactory purity. The reaction time of the test strips was between 5 to 10 minutes, with a detection limit for samples at 200 ng/mL. Both specificity and accuracy were satisfactory, and the test strip remained valid for 6 months. Conclusion A simple and rapid colloidal gold immunochromatography is established successfully for detecting several organophosphorus compounds and may be useful for on-site preliminary screening of samples in large quantities.

One-Dimensional Covalent Organic Framework with Improved Charge Transfer for Enhanced Electrochemiluminescence.

We present a dimensional regulating charge transfer strategy to achieve an enhanced electrochemiluminescence (ECL) by constructing a one-dimensional pyrene-based covalent organic framework (1D-COF). The dual-chain-like edge architecture in 1D-COF facilitates the stabilization of aromatic backbones, the enhancement of electronic conjugations, and the decrease of energy loss. The 1D-COF generates enhanced anodic (92.5-fold) and cathodic (3.2-fold) signals with tripropylamine (TPrA) and K2S2O8 as the anodic and cathodic coreactants, respectively, compared with 2D-COF. The anodic and cathodic ECL efficiencies of 1D-COF are 2.08- and 3.08-fold higher than those of 2D-COF, respectively. According to density functional theory (DFT), the rotational barrier energy (ΔE) of 1D-COF enhances sharply with the increase of dihedral angle, suggesting that the architecture in 1D-COF restrains the intramolecular spin of aromatic chains, which facilitates the decrease of nonradiative transitions and the enhancement of ECL. Furthermore, 1D-COF can be used to construct an ECL biosensor for sensitive detection of dopamine.

Excited-State Engineering Enables Efficient Deep-Blue Light-Emitting Diodes Exhibiting BT.2020 Color Gamut.

Organic luminescent materials that exhibit thermally activated delayed fluorescence (TADF) can convert non-emissive triplet excitons into emissive singlet states through a reverse intersystem crossing (RISC) process. Therefore, they have tremendous potential for applications in organic light-emitting diodes (OLEDs). However, with the development of ultra-high definition 4K/8K display technologies, designing efficient deep-blue TADF materials to achieve the Commission Internationale de l'Éclairage (CIE) coordinates fulfilling BT.2020 remains a significant challenge. Here, an effective approach is proposed to design deep-blue TADF molecules based on hybrid long- and short-range charge-transfer by incorporation of multiple donor moieties into organoboron multiple resonance acceptors. The resulting TADF molecule exhibits deep-blue emission at 414 nm with a full width at half maximum (FWHM) of 29 nm, together with a thousand-fold increase in RISC rate. OLEDs based on the champion material achieve a record maximum external quantum efficiency (EQE) of 22.8% with CIE coordinates of (0.163, 0.046), approaching the coordinates of the BT.2020 blue standard. Moreover, TADF-assisted fluorescence devices employing the designed material as a sensitizer exhibit an exceptional EQE of 33.1%. This work thus provides a blueprint for future development of efficient deep-blue TADF emitters, representing an important milestone towards meeting the blue color gamut standard of BT.2020.

A Case Report of Meigs' Syndrome Caused by Ovarian Fibrothecoma with High Levels of CA125.

Purpose: Meigs' syndrome is a rare gynecological disease characterized by the triad of benign ovarian tumor, ascites, and pleural effusion. Ovarian malignancies should be highly suspected in a postmenopausal woman with a pelvic mass, ascites, hydrothorax, and an elevated carbohydrate antigen 125 (CA125) level. It can be challenging to make a preoperative diagnosis of Meigs' syndrome. In this report, we present a case of Meigs' syndrome caused by an ovarian fibrothecoma and review the relevant literature to raise awareness and avoid misdiagnosis. Case Presentation: An 82-year-old woman with a 2-week history of abdominal distension was admitted to the Department of Gynecology. Ultrasound and thoracoabdominal computed tomography scans showed a left-sided hypoechoic mass in the pelvic cavity with bilateral pleural effusion and massive ascites. The CA125 concentration was 1040 U/mL (normal, 0-35 U/mL). With a working diagnosis of ovarian malignancy, the patient underwent ultrasound-guided fine-needle puncture of the pelvic mass and paracentesis to drain the ascites. The fine-needle puncture and paracentesis fluid analysis results revealed that the ascites did not contain any tumor cells, and the pelvic mass was identified as a spindle cell tumor. Immunohistochemistry confirmed that it was a sex-cord stromal tumor. Total abdominal hysterectomy and bilateral adnexectomy were performed under general anesthesia. The pathology results confirmed the mass to have been an ovarian fibrothecoma. At the 2-month postoperative follow-up, the ascites and hydrothorax had resolved and not recurred, and the CA125 level was normal. Conclusion: Despite the high suspicion of ovarian carcinoma in postmenopausal women presenting with pelvic mass, ascites, pleural effusion, and elevated CA125, Meigs' syndrome should be considered.

Folate-Targeted Nanocarriers Co-Deliver Ganciclovir and miR-34a-5p for Combined Anti-KSHV Therapy.

Kaposi's sarcoma-associated herpesvirus (KSHV) can cause a variety of malignancies. Ganciclovir (GCV) is one of the most efficient drugs against KSHV, but its non-specificity can cause other side effects in patients. Nucleic acid miR-34a-5p can inhibit the transcription of KSHV RNA and has great potential in anti-KSHV therapy, but there are still problems such as easy degradation and low delivery efficiency. Here, we constructed a co-loaded dual-drug nanocomplex (GCV@ZIF-8/PEI-FA+miR-34a-5p) that contains GCV internally and adsorbs miR-34a-5p externally. The folic acid (FA)-coupled polyethyleneimine (PEI) coating layer (PEI-FA) was shown to increase the cellular uptake of the nanocomplex, which is conducive to the enrichment of drugs at the KSHV infection site. GCV and miR-34a-5p are released at the site of the KSHV infection through the acid hydrolysis characteristics of ZIF-8 and the "proton sponge effect" of PEI. The co-loaded dual-drug nanocomplex not only inhibits the proliferation and migration of KSHV-positive cells but also decreases the mRNA expression level of KSHV lytic and latent genes. In conclusion, this co-loaded dual-drug nanocomplex may provide an attractive strategy for antiviral drug delivery and anti-KSHV therapy.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Conductive Hydrogel Dressing with High Mechanical Strength for Joint Wound Healing.

Hydrogel wound dressing can accelerate angiogenesis to achieve rapid wound healing, but traditional hydrogel dressings are difficult to meet the repair of joint sites due to their low mechanical strength. Therefore, we constructed the gel system by designing the chemical-physical interpenetrating network structure to achieve high strength and high toughness of the hydrogel. The high-strength double-network hydrogels were synthesized by simple free radical polymerization and low-temperature physicochemical cross-linking in our experiments. The suspension was obtained by green reduction of graphene oxide with carboxymethyl chitosan, followed by the introduction of acrylamide (AM) to form a covalent cross-linked network, which was immersed in ferric chloride solution to form metal ligand bonds, and finally the chemical-physical dual cross-linked network hydrogel wound dressing was prepared. Here, reduced graphene oxide can enhance electrical conductivity and excellent near-infrared photothermal effect to the hydrogel. The cell viability of this novel wound dressing was above 90.0%, its hemolysis rate was below 2.0%, and the electrical conductivity could reach (6.89 ± 0.07 (mS/cm)). In addition, the stress-strain curve demonstrated that the double cross-linked network hydrogel could reach a stress of more than 0.8 MPa at 82.0% strain, and the cyclic compression experiment shows that it can still recover its original shape after five times of repeated compression. This work can provide a reference for the exploitation of high mechanical strength hydrogel wound dressings with good electrical conductivity and near-infrared photothermal effect. This article is protected by copyright. All rights reserved.

The BHLHE40‒PPM1F‒AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer.

BHLHE40 is a basic helix-loop-helix transcription factor that is involved in multiple cell activities including differentiation, cell cycle, and epithelial-to-mesenchymal transition. While there is growing evidence to support the functions of BHLHE40 in energy metabolism, little is known about the mechanism. In this study, we found that BHLHE40 expression was downregulated in cases of endometrial cancer of higher grade and advanced disease. Knockdown of BHLHE40 in endometrial cancer cells resulted in suppressed oxygen consumption and enhanced extracellular acidification. Suppressed pyruvate dehydrogenase (PDH) activity and enhanced lactated dehydrogenase (LDH) activity were observed in the knockdown cells. Knockdown of BHLHE40 also led to dephosphorylation of AMPKα Thr172 and enhanced phosphorylation of pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) Ser293 and lactate dehydrogenase A (LDHA) Tyr10. These results suggested that BHLHE40 modulates PDH and LDH activity by regulating the phosphorylation status of PDHA1 and LDHA. We found that BHLHE40 enhanced AMPKα phosphorylation by directly suppressing the transcription of an AMPKα-specific phosphatase, PPM1F. Our immunohistochemical study showed that the expression of BHLHE40, PPM1F, and phosphorylated AMPKα correlated with the prognosis of endometrial cancer patients. Because AMPK is a central regulator of energy metabolism in cancer cells, targeting the BHLHE40‒PPM1F‒AMPK axis may represent a strategy to control cancer development.

Ultrathin-FeOOH-coated MnO2 nanozyme with enhanced catalase-like and oxidase-like activities for photoelectrochemical and colorimetric detection of organophosphorus pesticides.

Herein, we develop a dual-mode biosensor for photoelectrochemical and colorimetric detection of organophosphate pesticides (OPPs) based on ultrathin-FeOOH-coated MnO2 (MO@FHO) nanozyme. In this biosensor, OPPs can inhibit the alkaline phosphatase (ALP) activity and hinder the dephosphorylation of l-ascorbic acid-2-phosphate, preventing the decomposition of MO@FHO nanozyme and inducing both a photoelectrochemical (PEC) signal and the colorimetric change. The MO@FHO nanozyme not only possesses an enhanced catalase-like activity to degrade H2O2 for the generation of an improved cathodic photocurrent, but also exhibits an excellent oxidase-like activity to oxidize 3,3,5,5-tetramethylbenzidine with high catalytic efficiency. This biosensor displays a detection limit of 50 pmol/L for the PEC mode and a detection limit of 0.8 nmol/L for the colorimetric mode. Moreover, this biosensor exhibits excellent performance in complex biological matrices, and the smartphone-based visual sensing platform facilitates rapid and sensitive detection of OPPs, holding promising applications in food safety monitoring, and on-site detection.

RNA Condensate as a Versatile Platform for Improving Fluorogenic RNA Aptamer Properties and Cell Imaging.

Fluorogenic RNA aptamers are valuable tools for cell imaging, but they still suffer from shortcomings such as easy degradation, limited photostability, and low fluorescence enhancement. Molecular crowding conditions enable the stabilization of the structure, promotion of folding, and improvement of activity of functional RNA. Based on artificial RNA condensates, here we present a versatile platform to improve fluorogenic RNA aptamer properties and develop sensors for target analyte imaging in living cells. Using the CUG repeat as a general tag to drive phase separation, various fluorogenic aptamer-based RNA condensates (FLARE) were prepared. We show that the molecular crowding of FLARE can improve the enzymatic resistance, thermostability, photostability, and binding affinity of fluorogenic RNA aptamers. Moreover, the FLARE systems can be modularly engineered into sensors (FLARES), which demonstrate enhanced brightness and sensitivity compared to free sensors dispersed in homogeneous solution. This scalable design principle provides new insights into RNA aptamer property regulation and cellular imaging.

Synthesis of silica-encapsulated tetraphenylethylene with aggregation-induced electrochemiluminescence resonance energy transfer for sensitively sensing microcystin-LR.

The reported organic electrochemiluminescence (ECL) luminophors for the detection of various markers often suffer from intermolecular π-π stacking-induced luminophore quenching. Herein, we demonstrate one-pot synthesis of a new aggregation-induced electrochemiluminescence (AIECL) emitter (i.e., TPE@SiO2/rGO composite) for sensitive measurement of microcystin-leucine arginine (MC-LR). The TPE@SiO2/rGO composite is constructed by embedding the silica-encapsuled 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) in the reduced graphene oxide. In comparison with the monomer TPE, this composite exhibit high luminescence efficiency and strong ECL emission, because the AIECL phenomenon triggered by the spatial confinement effect in the SiO2 cage induces the restriction of the internal motion and vibration of molecules. Notably, this composite has distinct advantages of easy preparation, simple functionalization, and stable luminescence. Especially, the TPE@SiO2/rGO-based ECL-RET system exhibits a high quenching efficiency (ΦET) of 69.7%. When target MC-LR is present, it triggers DNA strand displacement reaction (SDR), inducing the quenching of the ECL signal of TPE@SiO2/rGO composite due to ECL resonance energy transfer between TPE@SiO2/rGO composite and methylene blue (MB). The proposed biosensor enables highly sensitive, low-cost, and robust measurement of MC-LR with a large dynamic range of 7 orders of magnitude and a detection limit of 3.78 fg/mL, and it displays excellent detection performance in complex biological matrices, holding potential applications in food safety and water monitoring.

Neoadjuvant versus adjuvant radiotherapy for resectable locally advanced gastric cancer: A SEER population analysis.

Background: There is a lack of evidence on whether resectable locally advanced gastric cancer (LAGC) patients could benefit from neoadjuvant or adjuvant radiotherapy (RT). Methods: Patients with surgically diagnosed LAGC from 2004 to 2015 were retrieved from the SEER database. Kaplan-Meier method and the log-rank test were used to evaluate survival analysis between neoadjuvant and adjuvant RT. Univariate Cox regression was used to evaluate the hazard ratio (HR) and 95 % confidence interval (CI). Results: A total of 4790 LAGC patients who treated with surgery and RT were identified, including 3187 patients with intestinal subtype and 1603 patients with diffuse subtype. For patients with both intestinal and diffuse subtypes, median cancer-specific survival (mCSS) was better with adjuvant RT or neoadjuvant RT. Moreover, patients benefited more from adjuvant RT than neoadjuvant RT (intestinal subtype: mCSS 49 vs. 36 months, P < 0.001; diffuse subtype: mCSS 32 vs. 26 months, P = 0.050). Further analyses showed that patients with intestinal subtype and T1-2N+, T3N-, T3N+ subgroups, as well as patients with diffuse subtype and T1-2N+ and T3N+ subgroups benefited more from adjuvant RT than those with neoadjuvant RT. Patients in the diffuse subtype and T3N- subgroups also tended benifit from adjuvant RT and survive. There was no difference in survival between the T4N- and T4N + subgroups of the two subtypes. After propensity score matching, subgroup analysis identified an improved survival in favor of adjuvant RT in the age ≥65 years and female subgroups in diffuse subtypes and T4N+ patients. Conclusions: For patients with resectable LAGC in the T1-2N+, T3N-, T3N+ clinical subgroups, adjuvant RT yields more benefits than neoadjuvant RT or no RT, which is worthy of prospective clinical trial.

Exogenous Co-Reactant-Free Electrochemiluminescent Biosensor for Ratiometric Measurement of α-Glucosidase Based on a ZIF-67-Regulated Hydrogen-Bonded Organic Framework.

The development of highly sensitive and selective analytical approaches for monitoring enzymatic activity is critical for disease diagnosis and biomedical research. Herein, we develop an exogenous co-reactant-free electrochemiluminescence (ECL) biosensor for the ratiometric measurement of α-glucosidase (α-Glu) based on a zeolitic imidazolate framework (ZIF-67)-regulated pyrene-based hydrogen-bonded organic framework (HOF-101). Target α-Glu can hydrolyze maltose to α-d-glucose, which can subsequently react with GOx to produce gluconic acid. The resultant gluconic acid can dissolve ZIF-67, leading to the recovery of the HOF-101 cathodic ECL signal and the decrease of the luminol anodic ECL signal. The long-range ordered structure of HOF-101 can speed up charge transfer, resulting in a stable and strong cathodic ECL signal. Moreover, ZIF-67 can not only efficiently quench the ECL signal of HOF-101 due to ECL resonance energy transfer between HOF-101 and ZIF-67 as well as the steric hindrance effect of ZIF-67 but also enhance the anodic ECL emission of luminol in dissolved O2 system because of its ordered and porous crystalline structure and the atomically dispersed Co2+. Notably, HOF-101 possesses a higher ECL efficiency (32.22%) compared with the Ru(bpy)32+ standard. Importantly, this ratiometric ECL biosensor shows high sensitivity (a detection limit of 0.19 U L-1) and a broad linear range (0.2-50 U L-1). This biosensor can efficiently eliminate systematic errors and enhance detection reliability without the involvement of exogenous co-reactants, and it displays good assay performance in human serum samples, holding great promise in biomedical research studies.

Synergistic Interaction between Metal Single-Atoms and Defective WO3- x Nanosheets for Enhanced Sonodynamic Cancer Therapy.

Although metal single-atom (SA)-based nanomaterials are explored as sonosensitizers for sonodynamic therapy (SDT), they normally exhibit poor activities and need to combine with other therapeutic strategies. Herein, the deposition of metal SAs on oxygen vacancy (OV)-rich WO3- x nanosheets to generate a synergistic effect for efficient SDT is reported. Crystalline WO3 and OV-rich WO3- x nanosheets are first prepared by simple calcination of the WO3 ·H2 O nanosheets under an air and N2 atmosphere, respectively. Pt, Cu, Fe, Co, and Ni metal SAs are then deposited on WO3- x nanosheets to obtain metal SA-decorated WO3- x nanocomposites (M-WO3- x ). Importantly, the Cu-WO3- x sonosensitizer exhibits a much higher activity for ultrasound (US)-induced production of reactive oxygen species than that of the WO3- x and Cu SA-decorated WO3 , which is also higher than other M-WO3- x nanosheets. Both the experimental and theoretical results suggest that the excellent SDT performance of the Cu-WO3- x nanosheets should be attributed to the synergistic effect between Cu SAs and WO3- x OVs. Therefore, after polyethylene glycol modification, the Cu-WO3- x can quickly kill cancer cells in vitro and effectively eradicate tumors in vivo under US irradiation. Transcriptome sequencing analysis and further molecular validation suggest that the Cu-WO3- x -mediated SDT-activated apoptosis and TNF signaling pathways are potential drivers of tumor apoptosis induction.

Theoretical insights into the mechanism underlying aflatoxin B1 transformation by the BsCotA-methyl syringate system.

Global concern exists regarding the contamination of food and animal feed with aflatoxin B1 (AFB1), which poses a threat to the health of both humans and animals. Previously, we found that a laccase from Bacillus subtilis (BsCotA) effectively detoxified AFB1 in a reaction mediated by methyl syringate (MS), although the underlying mechanism has not been determined. Therefore, our primary objective of this study was to explore the detoxification mechanism employed by BsCotA. First, the enzyme and mediator dependence of AFB1 transformation were studied using the BsCotA-MS system, which revealed the importance of MS radical formation during the oxidation process. Aflatoxin Q1 (AFQ1) resulting from the direct oxidation of AFB1 by BsCotA, was identified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results of UPLC-MS/MS and density functional theory calculations indicated that the products included AFQ1, AFB1-, and AFD1-MS-coupled products in the BsCotA-MS system. The toxicity evaluations revealed that the substances derived from the transformation of AFB1 through the BsCotA-MS mechanism exhibited markedly reduced toxicity compared to AFB1. Finally, we proposed a set of different AFB1-transformation pathways generated by the BsCotA-MS system based on the identified products. These findings greatly enhance the understanding of the AFB1-transformation mechanism of the laccase-mediator system.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

A rate-limiting step in antidepressants onset: Excitation of glutamatergic pyramidal neurons in medial prefrontal cortex of rodents.

Although clinical antidepressants have varied mechanisms of action, it remains unclear whether they may have a common mechanism underlying their antidepressant effects. We investigated the behavioral effects of five different antidepressants (differing in target, chemical structure, and rate of onset) and their effects on the firing activities of glutamatergic pyramidal neurons in the medial prefrontal cortex (mPFC) using the forced swimming test (FST) and electrophysiological techniques (in vivo). We employed fiber photometry recordings to validate the effects of antidepressants on the firing activity of pyramidal neurons. Additionally, multichannel electrophysiological recordings were conducted in mice exhibiting depressive-like behaviors induced by chronic restraint stress (CRS) to investigate whether antidepressants exert similar effects on pyramidal neurons in depressed mice. Behavioral tests were utilized for evaluating the depression model. We found that fluoxetine, duloxetine, vilazodone, YL-0919, and ketamine all increase the firing activities of glutamatergic pyramidal neurons (at least 57%) while exerting their initial onset of antidepressant effects. Fiber photometry revealed an increase in the calcium activity of pyramidal neurons in the mPFC at the onset of antidepressant effects. Furthermore, a significant reduction was observed in the firing activity of pyramidal neurons in the mPFC of CRS-exposed mice, which was reversed by antidepressants. Taken together, our findings suggested that five pharmacologically distinct classes of antidepressants share the common ability to increase the firing activity of pyramidal neurons, just different time, which might be a rate-limiting step in antidepressants onset. The study contributes to the body of knowledge of the mechanisms underlying antidepressant effects and paves the way for developing rapid-acting antidepressants.

False negative result of polymerase chain reaction in very early stages of acute retinal necrosis.

BACKGROUND: Viral nucleic acid testing of intraocular fluid using polymerase chain reaction (PCR) is a major laboratory examination in the diagnosis of acute retinal necrosis (ARN). Importantly, false negative PCR results may occur in several special situations. We reported a case of ARN with a negative PCR result in the aqueous humour in the very early stages of disease. CASE PRESENTATION: A female patient presented to the ophthalmologist with complaints of blurred vision and redness in her left eye. Her medical history included ARN in her right eye 10 years prior. Although the result of the aqueous viral analysis by PCR in her left eye was negative the first time (one day after the appearance of ocular symptoms), ARN in her left eye was presumed based on the clinical signs. With timely antiviral and anti-inflammatory treatments, the retinal lesions diminished. The viral load of herpes simplex virus (HSV) turned positive (7.25 × 103 copies/mL) one week later, increased to 2.49 × 105 copies/mL after three weeks, and finally turned negative about five weeks after the onset of disease. The initial HSV-IgG level in the aqueous humour was 0.01 U/mL and increased to 222.64 U/mL in the final sampling. CONCLUSIONS: The results of PCR analysis can be negative in the very early stages of ARN. Diagnosis of ARN should be made based on the clinical features, and antiviral treatments should not be delayed. Repeated PCR analysis of the aqueous humour is necessary to confirm the diagnosis and monitor the disease process.

Simple and biodegradable mesoporous silica nanocarriers for enhancing antitumor therapy through photochemical synergism.

The biosafety and degradability of nanocarriers have always been an important factor restricting their entry into the clinic. In this work, a new nano-system was prepared by coating the photothermal effect of dopamine-doped mesoporous silica nanoparticles with carboxymethyl chitin through electrostatic interaction, and is further anchored with folic acid on the surface for targeted delivery of anti-cancer the drug doxorubicin (DOX). The nano-system (DOX@PDA/MSN-CMCS-FA) is simply modified CMCS after being loaded with DOX and has good dispersibility, and the drug loading is 10.6%. In vitro release studies have shown that the release rate of PDA/MSN-CMCS-FA is 40% in pH 5.5. Effective degradation is debris in 14 d acidic environments. Due to the anti-infrared photothermal effects of PDA doping and DOX chemotherapy, the semi-lethal concentration (IC50) of nanoparticles (NPS) was 14.95 µg/mL, which can inhibit tumor cell growth by photochemical synergistic treatment, and have certain degradation performance.