Multi-Mechanism Antibacterial Strategies Enabled by Synergistic Activity of Metal-Organic Framework-Based Nanosystem for Infected Tissue Regeneration.

Drug-resistant bacterial infection impairs tissue regeneration and is a challenging clinical problem. Metal-organic frameworks (MOFs)-based photodynamic therapy (PDT) opens up a new era for antibiotic-free infection treatment. However, the MOF-based PDT normally encounters limited photon absorbance under visible light and notorious recombination of photogenerated holes and electrons, which significantly impede their applications. Herein, a MOFs-based nanosystem (AgNPs@MOFs) with enhanced visible light response and charge carrier separation is developed by modifying MOFs with silver nanoparticles (AgNPs) to improve PDT efficiency. The AgNPs@MOFs with enhanced photodynamic performance under visible light irradiation mainly disrupt bacteria translation process and the metabolism of purine and pyrimidine. In addition, the introduction of AgNPs endows nanosystems with chemotherapy ability, which causes destructive effect on bacterial cell membrane, including membrane ATPase protein and fatty acids. AgNPs@MOFs show excellent synergistic drug-resistant bacterial killing efficiency through multiple mechanisms, which further restrain bacterial resistance. In addition, biocompatible AgNPs@MOFs pose potential tissue regeneration ability in both Methicillin-resistant Staphylococcus aureus (MRSA)-related soft and hard tissue infection. Overall, this study provides a promising perspective in the exploration of AgNPs@MOFs as nano antibacterial medicine against drug-resistant bacteria for infected tissue regeneration in the future.

pH-Triggered Size-Tunable Silver Nanoparticles: Targeted Aggregation for Effective Bacterial Infection Therapy.

The rapid spread of drug-resistant pathogens threatens human health. To address the current antibacterial dilemma, the development of antibiotic-free strategies using nanotechnology is imperative. In this study, silver nanoparticles (Ag-P&C NPs) with pH-sensitive charge reversal and self-aggregation capacities are successfully synthesized. In the acidic microenvironment of bacterial biofilms, protonation of the surface peptide enhances the affinity of Ag-P&C NPs for bacteria, which can make Ag-P&C NPs prone to target and penetrate into biofilms, and the self-aggregated capacity helps Ag-P&C NPs remain in biofilms for a long time to disrupt bacterial biofilm formation. In addition, biocompatible Ag-P&C NPs are utilized in three types of bacteria-infected animal models. They exhibit an excellent performance in killing bacteria, inhibiting plaque biofilms, and ameliorating inflammatory responses. In conclusion, this study offers new insights into antibiotic-free antibacterial strategies, and exhibits promising application prospects.

A single-center experience of parathyroidectomy in 1500 cases for secondary hyperparathyroidism: a retrospective study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. With the deterioration of renal function, a certain proportion of CKD patients enter the uremic stage, and secondary hyperparathyroidism (SHPT) becomes a challenge. For refractory hyperparathyroidism, parathyroidectomy (PTX) plays a key role in reducing mortality and improving prognosis. Nevertheless, no consensus has been reached on the optimal surgical method. We aimed to provide evidence for the effectiveness of surgical treatment by summarizing the experience from our center. METHODS: Clinical data from 1500 patients undergoing parathyroidectomy were recorded, which included 1419 patients in a total parathyroidectomy without autotransplantation (tPTX) group, 54 patients in a total parathyroidectomy plus autotransplantation (tPTX + AT) group, and 27 patients in the other group. Perioperative basic data, intact parathyroid hormone (i-PTH) levels, serum calcium levels, serum phosphorus levels, pathological reports, coexisting thyroid diseases, short-term outcomes and complications were analyzed. Moreover, postoperative complications were compared between the tPTX and tPTX + AT groups. RESULTS: Parathyroid hormone, serum calcium and phosphorus levels decreased significantly post-surgery. Two patients died during the perioperative period. As the two most common complications, the incidences of severe hypocalcemia and hyperkalemia were 36.20% (543 cases) and 24.60% (369 cases), respectively. Pre-iPTH levels (OR = 1.001, 95% CI: 1.001-1.001, p < 0.01), serum alkaline phosphatase (ALP) levels (OR = 1.002, 95% CI: 1.001-1.002, p < 0.01) and the mass of excised parathyroid gland (OR = 3.06, 95% CI: 1.24-7.55, p = 0.02) were positively associated with postoperative severe hypocalcemia, while age and serum calcium were negatively associated with it. Pathological reports of resected parathyroid and thyroid glands indicated that 96.49% had parathyroid nodular hyperplasia, 13.45% had thyroid nodular hyperplasia, and 4.08% had thyroid papillary carcinoma. CONCLUSIONS: Parathyroidectomy is a safe and effective treatment for refractory secondary hyperparathyroidism. Severe hypocalcemia is the main complication, and coexistent thyroid diseases should never be neglected.

Arabidopsis SMAX1 overaccumulation suppresses rosette shoot branching and promotes leaf and petiole elongation.

ARABIDOPSIS: SMAX1/SMXL (SUPPRESSOR OF MAX2 1/SMAX1-LIKE) proteins function as transcriptional repressors in karrikin and strigolactone (SL) signaling pathways and regulate plant architecture. MAX2 is a common factor in the two signaling pathways and a component of the SCF complex that modulates the proteasome-mediated degradation of SMAX1/SMXLs. SMXL6, 7, and 8 proteins promote shoot branching and inhibit petiole elongation. Our study found that the accumulation of SMAX1 suppresses rosette shoot branching and increases cauline branches on the primary inflorescence stem, plant height, petiole length, and leaf length/width ratio. The SMAX1 accumulation enhances the expression of BRC1, HB53, HB40, and HB21 that modulate shoot branching. SMAX1 also regulates the expression of the genes involved in auxin transport, cytokinin signaling pathway, and SL biosynthesis. The expression analyses of these genes suggest that excessive SMAX1 should accelerate the transport of auxin and the biosynthesis of SL in plants. High SL concentration suppresses the bud development in smax1D mutant that accumulates SMAX1 protein in plant. However, the effects of cytokinin and auxin on shoot branching remain elusive in the mutant with excessive SMAX1. SMAX1 regulates leaf shape and petiole length via modulating TCP1 expression. Our findings reveal a novel function of SMAX1 and new mechanism of shoot branching.

Adsorption of soluble microbial products by sediments.

As major precursors of disinfection by-products (DBPs), soluble microbial products (SMPs) generated by sewage discharge can adversely affect drinking water quality. It is essential to understand the adsorption behaviours of SMPs onto sediments and the effect of DBPs formation. In this study, the adsorption ability of sediments was evaluated by adsorption isotherms with respect to temperature and salinity. Adsorption behaviours were investigated using X-ray photoelectron spectroscopy, electron microscopy analysis, and excitation emission matrix fluorescence analysis. Chlorination was also employed to explore the influence of sediment adsorption on drinking water quality. The results indicated that the maximum adsorption potential of sediments to SMPs was 1.60 mg/g, which involved exothermic processes. SMPs adsorption declined with increasing temperature and salinity, and fulvic acid and protein in SMPs were more readily adsorbed on sediments than was humic acid. Correlation analysis results indicated that adsorption behaviours of sediments to SMPs could significantly reduce the generation potential of DBPs (r = 0.882-0.938, p < 0.01). In addition, the decrease of C-DBPs was considerably greater than that of N-DBPs. These research findings are of importance to assessments of the fate and transport of SMPs in water-sediment systems, as well as the effect of following DBPs formation in the drinking water supply.

Copper-resistant mechanism of Ochrobactrum MT180101 and its application in membrane bioreactor for treating electroplating wastewater.

It is necessary to study the mechanism of resistance to heavy metals in microbiological processes. In this study, Ochrobactrum MT180101 was used as the microbial source of an membrane bioreactor to investigate its degradation efficiency for electroplating wastewater and the copper-resistant mechanism. Meanwhile, excitation emission matrix-parallel factor, scanning electron microscope, atomic force microscope, fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and proteome analyses were applied to explain the comprehensive mechanism of the Ochrobactrum MT180101 resisting heavy metal toxicity. The results indicated that the Ochrobactrum MT180101 resisted heavy metal toxicity with the following pathways: i) binding metal cations on cell wall surfaces, ii) generating microbial products such as protein to chelate and stabilize the metal cations, iii) bio-transporting heavy metals from the intramembrane to the outer membrane by means of intracellular transport, and iv) reducing heavy metals through enzyme-mediated biotransformation. The results ensure that Ochrobactrum MT180101 was a copper-resistant bacterium that can be used in the pretreatment or deep treatment of electroplating wastewater.

Biosorption behavior of the Ochrobactrum MT180101 on ionic copper and chelate copper.

To study the biosorption behaviors of bacteria on heavy metal chelators, the biosorption kinetics, biosorption thermodynamics and pH influence tests of the Ochrobactrum MT180101 on ionic and chelate copper were investigated. Furthermore, the biosorption mechanisms of the Ochrobactrum MT180101 on ionic copper and chelate copper were explained by means of an excitation emission matrix as well as infrared and X-ray photoelectron spectroscopy. The results indicated the following. 1) The biosorption on chelate copper was needed to destroy the complexation group first through metabolic and secretory activities. 2) The biosorption mechanism of the Ochrobactrum MT180101 on copper involved surface biosorption, extracellular chelation and bienzyme-mediated biotransformation. The results suggested that Ochrobactrum had a superior biosorption efficiency to ionic and chelate copper.

Case Report: Acute Hydrops with Descemet Membrane Schisis in Corneal Ectasia after Radial Keratotomy.

SIGNIFICANCE: As patients with previous radial keratotomy (RK) are still occasionally encountered, recognition of the anatomy of post-RK corneas and management of their complications remain relevant. High-definition anterior segment optical coherence tomography (AS-OCT) is a very useful tool to assess these postsurgical corneas. PURPOSE: To describe a case of acute corneal hydrops with Descemet membrane schisis after RK with observation by AS-OCT. CASE REPORT: A 43-year-old woman presented with a 9-day history of sudden vision loss, foreign body sensation, and photophobia in her left eye. She had undergone bilateral RK 25 years ago at her local hospital. Slit-lamp examination revealed marked corneal edema and stromal clefts in the central cornea along with radial surgical scars in her left eye. Pentacam imaging showed the typical pattern of a post-RK cornea with ectasia in her right eye. Multiple dilacerations of collagen lamellae and fluid-filled intrastromal cysts together with epithelial edema were observed in her left eye using AS-OCT. A Descemet membrane detachment with schisis was also shown by AS-OCT. After 5 months of medication with topical 0.1% fluorometholone eye drops four times daily together with 3% ofloxacin eye ointment once daily, the corneal edema, Descemet membrane detachment, and Descemet membrane schisis had completely resolved resulting in pan-stromal scarring. CONCLUSIONS: This report describes acute corneal hydrops with Descemet membrane schisis after RK imaged using high-definition AS-OCT. The acute hydrops was possibly caused by corneal ectasia or underlying keratoconus, which was aggravated by RK. High-definition AS-OCT is a useful tool to demonstrate the details of different corneal layers and to observe the resolving process of acute hydrops. Topical medications consisting of antibiotic, lubrication, and corticosteroid can be used to treat the acute event effectively.

Assessment of Tear Film and Bulbar Redness by Keratograph 5M in Pediatric Patients After Orthokeratology.

OBJECTIVES: To assess the tear meniscus height (TMH), noninvasive tear breakup time (NITBUT), and bulbar redness in pediatric patients after orthokeratology (OK). METHODS: Pediatric patients who underwent overnight OK between December 2014 and November 2017 were retrospectively investigated. According to the time of wearing, subjects were divided into three groups: 1-week, 1-month, and over 1-year. Age-matched subjects were recruited as a control group. Keratograph 5M was used to assess TMH, NITBUT-first, NITBUT-average, and bulbar redness score. RESULTS: A total of 106 subjects aged from 7 to 15 years were included. Compared with control group, NITBUT-first was significantly lower in 1-week group (P=0.036) and NITBUT-average was significantly lower in 1-month group (P=0.019). Compared with over 1-year group, NITBUT-first was significantly lower in 1-week and 1-month groups (P=0.014, P=0.035, respectively), and NITBUT-average was significantly lower in 1-month group (P=0.022). Bulbar redness score was significantly lower in 1-month group than 1-week group (P=0.004). No significant difference in TMH was found between all groups. Significant correlation was found between NITBUT-first and NITBUT-average in all subjects (R=0.812, P<0.001). No other significant correlations were found between variables included TMH, NITBUT, bulbar redness score, or target correction. CONCLUSIONS: As a noninvasive method, Keratograph 5M was easily to be applied on pediatric patients. The OK lens did not induce significant tear deficiency or bulbar redness, but might affect tear film stability in a short term after wearing.

Descemet's Membrane Detachment with Schisis Induced by Phacoemulsification.

PURPOSE: To describe a case of Descemet's membrane detachment and schisis (Descemet's membrane separated into multiple layers) with confirmation by high-definition anterior segment optical coherence tomography (AS-OCT) after phacoemulsification and intraocular lens implantation. CASE REPORT: A 72-year-old woman presented with persistent corneal edema after phacoemulsification. She was diagnosed with herpes simplex keratitis and had been unsuccessfully treated for 60 days in her local hospital. Slit-lamp examination revealed moderate conjunctival injection, disciform-like stromal edema, and diffuse superficial punctate epithelial erosions. Descemet's membrane schisis and detachment with an interlayer tear were verified by high-definition AS-OCT. After 2 weeks of medication with topical 0.1% fluorometholone eye drops four times daily together with 3% ofloxacin eye ointment twice daily, Descemet's membrane was reattached with complete resolution of conjunctival injection, corneal edema, and epithelial erosions. CONCLUSIONS: This is a report of Descemet's membrane schisis in vivo that is documented and confirmed by high-definition AS-OCT. Descemet's membrane detachment and schisis caused by phacoemulsification can be misdiagnosed as herpetic keratitis due to stromal edema and epithelial erosion. Topical steroid and lubrication may help reattach Descemet's membrane to its original position.

Effects of Long-term Soft Contact Lenses on Tear Menisci and Corneal Nerve Density.

PURPOSE: We investigated the relationship between tear menisci and corneal subbasal nerve density (SND) in long-term soft contact lens (CL) wearers. METHODS: Three groups were enrolled for this study: asymptomatic non-CL controls (N-CL group), asymptomatic soft CL wearers (A-CL group), and symptomatic soft CL wearers with self-reported moderate to severe dryness (S-CL group). Upper and lower tear menisci height (UTMH, LTMH) and area (UTMA, LTMA) were measured by optical coherence tomography. This was followed by measurements of fluorescein tear breakup time, fluorescein staining, and the Schirmer I test. In vivo confocal microscopy measured the SND in the nasal, central, and temporal regions of the cornea. RESULTS: The UTMH, UTMA, LTMH, and LTMA were significantly lower in the S-CL group compared with the N-CL group (P<0.05). The combined corneal SND of the temporal and nasal regions of the S-CL group was lower than for the N-CL group (P<0.05). The LTMH was correlated with the SND of the temporal (r=0.410), nasal (r=0.423), combined temporal and nasal (r=0.516), and combined temporal, nasal, and central regions (r=0.430, all P<0.01). The LTMA was also correlated with the SND of the temporal (r=0.379), nasal (r=0.292), combined temporal and nasal (r=0.422), and combined temporal, nasal, and central regions (r=0.367, all P<0.05). The temporal and nasal corneal SNDs were more strongly correlated with the LTMH and LTMA than with the UTMH and UTMA. CONCLUSIONS: Soft CL wearers with dry eye symptoms have reduced tear menisci. The alteration of midperipheral corneal SND may contribute to dry eye symptoms.

[Evaluation of tear film and meibomian gland function in dry eye patients using Keratograph 5M].

Objective: To assess the application of Keratograph 5M in evaluating tear film and meibomian gland function in patients with dry eye. Methods: A total of 144 eyes were recruited in the study, in which 72 eyes were from patients diagnosed with dry eye and 72 eyes were from healthy subjects. All subjects finished following tests or examinations:ocular surface disease index (OSDI) to evaluate eye symptoms; Keratograph 5M examination to obtain tear meniscus height (TMH), noninvasive tear break-up time (NIBUT) including first NIBUT (NIBUT-Fir) and average NIBUT (NIBUT-Ave), and infrared meibography; and fluorescein sodium staining to obtain fluorescein tearbreak-up time (FBUT). Results: Dry eye group had higher OSDI score than healthy control group, but its TMH, NIBUT-Fir and NIBUT-Ave were lower than those in healthy control group (all P<0.01). Total meiboscore in dry eye group was higher than that in healthy control group (P<0.01), and it showed a significant correlation with NIBUT-Fir and NIBUT-Ave (r=-0.449 and -0.398, P<0.01), but no correlation with ages was observed (r=0.031, P>0.05). The NIBUT-Fir and NIBUT-Ave showed a significant correlation with FBUT (r=0.833 and 0.727, P<0.01). Conclusion: Keratograph 5M is a convenient, accurate and non-invasive method to assess the function of tear film and meibomian gland, and the new meibography scoring system can evaluate the function of meibomian gland objectively and succinctly.

Tear menisci and corneal subbasal nerve density in patients after laser in situ keratomileusis.

OBJECTIVE: To investigate the relationship between tear menisci and corneal nerve density in patients after laser in situ keratomileusis (LASIK). METHODS: Twenty-eight eyes of 14 myopic patients were enrolled. Height and area of the upper and lower tear menisci--upper tear meniscus height, upper tear meniscus area, lower tear meniscus height (LTMH), and lower tear meniscus area (LTMA)--were measured by spectral domain optical coherence tomography before surgery, 1 week, 1 month, and 3 months after surgery. Central, temporal, and nasal corneal nerve densities were measured by confocal microscopy before surgery, 1 month, and 3 months after surgery. RESULTS: After surgery, LTMH and LTMA increased significantly from 1 week to 1 month (P=0.009 and =0.011, respectively) and 1 month to 3 months (P=0.003 and =0.039, respectively); temporal and nasal nerve densities increased significantly from 1 month to 3 months (P<0.001, P=0.016, respectively). Lower tear meniscus area was significantly correlated with central and nasal nerve densities at 1 month (R=0.478 and 0.46, P=0.01 and 0.014, respectively), whereas LTMH and LTMA at 3 months were significantly correlated with central nerve density at 1 month (R=0.449 and 0.608, P=0.017 and 0.001, respectively). CONCLUSIONS: Lower tear menisci and peripheral corneal nerves recovered continually after LASIK during the early stage. However, tear volume might depend on residual central corneal nerves at 1 month, rather than on corneal nerve recovery.

[Corneal subbasal nerve density changes after laser in situ keratomileusis with mechanical microkeratome and femtosecond laser].

OBJECTIVE: To compare the corneal subbasal nerve density (SND) changes after laser in situ keratomileusis (LASIK) with a microkeratome and a femtosecond laser. METHODS: Prospective clinical study. Sixty eyes of thirty myopes were included. Fifteen patients (30 eyes) underwent LASIK with the Moria II microkeratome, and the other 15 patients (30 eyes) with the 60 k Hz IntraLase femtosecond laser. Central, temporal and nasal corneal SNDs were measured by confocal microscopy and compared before surgery, 1 month, and 3 months after surgery. Analysis of variance and t test were used for comparing the differences between different time points and two groups. RESULTS: Preoperatively and 1 month, 3 months postoperatively, the SNDs were (16 728.30 ± 4 300.30), (1 875.42 ± 300.50) and (1 701.55 ± 194.11) µm/mm(2) in the central cornea, (11 379.70 ± 1 833.92), (1 341.20 ± 288.68) and (1 860.87 ± 147.60) µm/mm(2) in the temporal cornea, and (8 506.79 ± 662.83), (7 428.96 ± 712.99) and (8 044.32 ± 1 077.54) µm/mm(2) in the nasal cornea, respectively, in the microkeratome group, and (16 351.59 ± 3 503.88), (1 859.38 ± 452.93) and (2 043.67 ± 377.76) in the central cornea, (12 328.22 ± 2 007.43), (1 483.85 ± 371.28) and (2 126.31 ± 279.87) µm/mm(2) in the temporal cornea, and (8 347.91 ± 789.44), (1 475.53 ± 293.98) and (2 022.10 ± 282.89) µm/mm(2) in the nasal cornea, respectively, in the femtosecond laser group. The SNDs at three positions all decreased significantly at each time point postoperatively compared to the baseline values in both groups (1 and 3 months in the microkeratome group: central t = 18.981 and 18.912, temporal t = 30.121 and 27.921, and nasal t = 6.456 and 2.126; in the femtosecond laser group: central t = 22.667 and 22.379, temporal t = 29.000 and 28.376, and nasal t = 46.329 and 41.751; all P < 0.01, except 3 months at the nasal in the microkeratome group, P = 0.042). The nasal SND increased significantly from month 1 to month 3 (t = -3.921, P < 0.01) in the microkeratome group, and the temporal and nasal SNDs both increased significantly from month 1 to month 3 (t = -9.629 and -6.645, both P < 0.01) in the femtosecond group. There were no significant differences in the central SND between the two groups (F = 0.002, P = 0.96). Significant differences were found in the nasal SND between the groups at 1 month and 3 months (t = 42.281 and 29.608, both P < 0.01), and in the temporal SND at 3 months after surgery (t = -4.595, P < 0.01). CONCLUSIONS: Peripheral corneal nerve recovery occurred at 1 month after LASIK surgery. Patients with a femtosecond laser showed better corneal regeneration than those with a microkeratome.

Postmastectomy radiotherapy in breast reconstruction: Current controversies and trends.

Breast cancer is the most common cancer among women worldwide. Postmastectomy radiotherapy (PMRT) is an essential component of combined therapy for early-stage, high-risk breast cancer. Breast reconstruction (BR) is often considered for patients with breast cancer who have undergone mastectomy. There has been a considerable amount of discussion about the optimal approach to combining PMRT with BR in the treatment of breast cancer. PMRT may increase the risk of complications and prevent good aesthetic results after BR, while BR may increase the complexity of PMRT and the radiation dose to surrounding normal tissues. The purpose of this review is to give a broad overview and summary of the current controversies and trends in PMRT and BR in the context of the most recent literature available.

Accelerated partial breast irradiation: Current evidence and future developments.

Whole breast irradiation after breast-conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery. Accelerated partial breast irradiation (APBI) as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research. APBI is characterised by simple high-dose local irradiation of the tumour bed in a short time, thus improving convenience for patients and saving costs. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI.

Developing a Selection Framework for Zinc Ion-Based Biomaterial Design: Guided by the Biosafety Assessment of ZIF-8 and ZnO.

In recent years, nanomaterials have gained widespread use in the biomedical field, with ZIF-8 and ZnO emerging as promising candidates due to their remarkable performance in osteogenesis, angiogenesis, and antimicrobial therapy. However, before advancing these nanomaterials for clinical applications, it is imperative to evaluate their biocompatibility. In particular, comparing nanomaterials with similar biomedical functions is crucial for identifying the most suitable nanomaterials for further development and market entry. Our study aimed to compare the biocompatibility of nano-ZIF-8 and nano-ZnO under the same conditions. We found that nano-ZIF-8 exhibited lower toxicity both in vitro and in vivo compared to nano-ZnO. To gain insights into the underlying mechanisms responsible for this difference, we conducted further experiments to investigate lysosome damage, mitochondrial change, and the occurrence of ferroptosis. Additionally, we performed transcriptome sequencing to analyze the expression of relevant genes, thereby providing robust validation for our findings. In summary, our study highlighted the importance of evaluating nanomaterials with similar biomedical effects. Through this comparative study, we have not only shed light on the superior biocompatibility of nano-ZIF-8 over nano-ZnO, but also contributed valuable insights and methodological references for future material screening endeavors. Ultimately, our study served as a stepping stone toward the development of safer and more effective nanomaterials for various biomedical applications.

LanCL1 protects developing neurons from long-term isoflurane anesthesia-induced neurotoxicity.

Research has revealed that prolonged or repeated exposure to isoflurane, a common general anesthetic, can lead to cognitive and behavioral deficiencies, particularly in early life. The brain contains a wealth of LanCL1, an antioxidant enzyme that is thought to mitigate oxidative stress. Nevertheless, its precise function in mammals remains uncertain. This study uncovered a decrease in the expression of LanCL1 due to prolonged isoflurane anesthesia, accompanied by anesthesia-induced neurotoxicity in vivo and in vitro. To better understand LanCL1's essential function, LanCL1 overexpressing adenoviruses were employed to increase LanCL1 levels. The outcomes were analyzed using western blot and immunofluorescence methods. According to the findings, extended exposure to isoflurane anesthesia may lead to developmental neurotoxicity in vivo and in vitro. The anesthesia-induced neurotoxicity was concomitant with a reduction in LanCL1 expression. Moreover, the study revealed that overexpression of LanCL1 can mitigate the neurotoxic effects of isoflurane anesthesia, resulting in improved synaptic growth, less reactive oxygen species enhanced cell viability and rescued memory deficits in the developing brain. In conclusion, prolonged anesthesia-induced LanCL1 deficiency could be responsible for neurotoxicity and subsequent cognitive impairments in the developing brain. Additional LanCL1 counteracts this neurotoxic effect and protects neurons from long-term isoflurane anesthesia.

A knowledge-enhanced transform-based multimodal classifier for microbial keratitis identification.

Microbial keratitis, a nonviral corneal infection caused by bacteria, fungi, and protozoa, is an urgent condition in ophthalmology requiring prompt treatment in order to prevent severe complications of corneal perforation and vision loss. It is difficult to distinguish between bacterial and fungal keratitis from image unimodal alone, as the characteristics of the sample images themselves are very close. Therefore, this study aims to develop a new deep learning model called knowledge-enhanced transform-based multimodal classifier that exploited the potential of slit-lamp images along with treatment texts to identify bacterial keratitis (BK) and fungal keratitis (FK). The model performance was evaluated in terms of the accuracy, specificity, sensitivity and the area under the curve (AUC). 704 images from 352 patients were divided into training, validation and testing set. In the testing set, our model reached the best accuracy was 93%, sensitivity was 0.97(95% CI [0.84,1]), specificity was 0.92(95% CI [0.76,0.98]) and AUC was 0.94(95% CI [0.92,0.96]), exceeding the benchmark accuracy of 0.86. The diagnostic average accuracies of BK ranged from 81 to 92%, respectively and those for FK were 89-97%. It is the first study to focus on the influence of disease changes and medication interventions on infectious keratitis and our model outperformed the benchmark models and reaching the state-of-the-art performance.

Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury.

An important pathophysiological process of acute kidney injury (AKI) is mitochondrial fragmentation in renal tubular epithelial cells, which leads to cell death. Pyruvate kinase M2 (PKM2) is an active protein with various biological functions that participates in regulating glycolysis and plays a key role in regulating cell survival. However, the role and mechanism of PKM2 in regulating cell survival during AKI remain unclear. Here, we found that the phosphorylation of PKM2 contributed to the formation of the PKM2 dimer and translocation of PKM2 into the mitochondria after treatment with staurosporine or cisplatin. Mitochondrial PKM2 binds myosin heavy chain 9 (MYH9) to promote dynamin-related protein 1 (DRP1)-mediated mitochondrial fragmentation. Both in vivo and in vitro, PKM2-specific loss or regulation PKM2 activity partially limits mitochondrial fragmentation, alleviating renal tubular injury and cell death, including apoptosis, necroptosis, and ferroptosis. Moreover, staurosporine or cisplatin-induced mitochondrial fragmentation and cell death were reversed in cultured cells by inhibiting MYH9 activity. Taken together, our results indicate that the regulation of PKM2 abundance and activity to inhibit mitochondrial translocation may maintain mitochondrial integrity and provide a new therapeutic strategy for treating AKI.