Visual and Real-Time Monitoring of Cd2+ in Water, Rice, and Rice Soil with Test Paper Based on [2 + 2] Lanthanide Clusters.

Cadmium ions (Cd2+) are highly toxic to animal and human health, especially through the drinking of Cd2+-contaminated water and eating Cd2+-contaminated rice. Therefore, accurate detection of Cd2+ in water, rice, and rice soil is urgent. In this work, two [2 + 2] lanthanide clusters of Tb2Tb2 and Eu2Eu2 were synthesized and characterized in detail. Interestingly, Tb2Tb2 is a rapid sensor for Cd2+ through luminescence "turn-off". Further studies show that Tb2Tb2 is a highly sensitive and selective sensor toward Cd2+ in water, rice supernatants, and rice soil supernatants, with a very short response time of 20 s. The limit of detection (LOD) in the above three real samples is as low as 0.0112, 1.1240, and 0.1124 ppb, respectively, which is lower than the national standards for food safety in China (GB 2762-2022). More interestingly, a portable sensing device of test paper based on Tb2Tb2 is developed with a facile method, which shows visible, highly sensitive, and selective sensing toward Cd2+ in real samples of water, rice supernatants, and rice soil supernatants. Tb2Tb2 and its sensing device of test paper are an on-site analysis sensor for potentially non-expert users, especially for people in remote rural areas.

The efficacy and safety of micropulse transscleral laser treatment in glaucoma: a systematic review and meta-analysis.

OBJECTIVE: Micropulse transscleral laser treatment (mTLT) is the latest alternative intraocular pressure (IOP) lowering approach for glaucoma patients. This meta-analysis aims to evaluate the efficacy and safety of mTLT and continuous wave transscleral cyclophotocoagulation (CW-TSCPC) for the treatment of glaucoma. METHODS: We searched the PubMed, Embase, and Cochrane Library of Systematic Reviews databases from January 2000 to July 2022 to identify studies that, evaluated the efficacy and safety of mTLT in glaucoma. There were no restrictions regarding study type, patient age, or type of glaucoma. We analysed the reduction in IOP and the number of anti-glaucoma medications (NOAM), retreatment rates, and complications between mTLT and CW-TSCPC treatment. Publication bias was conducted for evaluating bias. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) reporting guideline. RESULTS: We identified 6 eligible studies of which only 2 RCTs and 386 participants with various types of glaucoma at different stages were ultimately included. The results revealed significant IOP decreases after mTLT up to 12 months and significant NOAM reductions at 1 month (WMD=-0.30, 95% CI -0.54 to 0.06), and 3 months (WMD=-0.39, 95% CI -0.64 to 0.14) in mTLT compared to CW-TSCPC. Moreover, the retreatment rates (Log OR=-1.00, 95% CI -1.71 to -0.28), hypotony (Log OR=-1.21, 95% CI -2.26 to -0.16), prolonged inflammation or uveitis (Log OR=-1.63, 95% CI -2.85 to -0.41), and worsening of visual acuity (Log OR=-1.13, 95% CI -2.19 to 0.06) occurred less frequently after mTLT. CONCLUSION: Our results demonstrated that mTLT could lower the IOP until 12 months after treatment. mTLT seems to have a lower risk of retreatment after the first procedure, and mTLT is superior to CW-TSCPC with respect to safety. Studies with longer follow-up durations and larger sample sizes are necessary in the future. TRIAL REGISTRATION NUMBER: INPLASY202290120.

Detection of a novel PAX6 variant in a Chinese family with multiple ocular abnormalities.

BACKGROUND: Aniridia is a congenital, panocular disease that can affect the cornea, anterior chamber angle, iris, lens, retina and optic nerve. PAX6 loss-of-function variants are the most common cause of aniridia, and variants throughout the gene have been linked to a range of ophthalmic abnormalities. Furthermore, particular variants at a given site in PAX6 lead to distinct phenotypes. This study aimed to characterize genetic variants associated with congenital aniridia in a Chinese family. METHODS: The proband and family underwent ophthalmologic examinations. DNA was sampled from the peripheral blood of all 6 individuals, and whole-exome sequencing was performed. Sanger sequencing was used to verify the variant in this family members. RESULTS: A novel variant (c.114_119delinsAATTTCC: p.Pro39llefsTer17) in the PAX6 gene was identified in subjects II-1, III-1 and III-2, who exhibited complete aniridia and cataracts. The proband and the proband's brother also had glaucoma, high myopia, and foveal hypoplasia. CONCLUSIONS: We identified that a novel PAX6 frameshift heterozygous deletion variant is the predominant cause of aniridia in this Chinese family. TRIAL REGISTRATION: We did not perform any health-related interventions for the participants.

Design of a novel stimulation system with time-varying paradigms for investigating new modes of high frequency stimulation in brain.

BACKGROUND: Deep brain stimulation (DBS) has shown wide clinical applications for treating various disorders of central nervous system. High frequency stimulation (HFS) of pulses with a constant intensity and a constant frequency is typically used in DBS. However, new stimulation paradigms with time-varying parameters provide a prospective direction for DBS developments. To meet the research demands for time-varying stimulations, we designed a new stimulation system with a technique of LabVIEW-based virtual instrument. METHODS: The system included a LabVIEW program, a NI data acquisition card, and an analog stimulus isolator. The output waveforms of the system were measured to verify the time-varying parameters. Preliminary animal experiments were run by delivering the HFS sequences with time-varying parameters to the hippocampal CA1 region of anesthetized rats. RESULTS: Verification results showed that the stimulation system was able to generate pulse sequences with ramped intensity and hyperbolic frequency accurately. Application of the time-varying HFS sequences to the axons of pyramidal cells in the hippocampal CA1 region resulted in neuronal responses different from those induced by HFS with constant parameters. The results indicated important modulations of time-varying stimulations to the neuronal activity that could prevent the stimulation from inducing over-synchronized firing of population neurons. CONCLUSIONS: The stimulation system provides a useful technique for investigating diverse stimulation paradigms for the development of new DBS treatments.

[High frequency stimulations change the phase-locking relationship between neuronal firing and the rhythms of field potentials].

Deep brain stimulation (DBS) has been successfully used to treat a variety of brain diseases in clinic. Recent investigations have suggested that high frequency stimulation (HFS) of electrical pulses used by DBS might change pathological rhythms in action potential firing of neurons, which may be one of the important mechanisms of DBS therapy. However, experimental data are required to confirm the hypothesis. In the present study, 1 min of 100 Hz HFS was applied to the Schaffer collaterals of hippocampal CA1 region in anaesthetized rats. The changes of the rhythmic firing of action potentials from pyramidal cells and interneurons were investigated in the downstream CA1 region. The results showed that obvious θ rhythms were present in the field potential of CA1 region of the anesthetized rats. The θ rhythms were especially pronounced in the stratum radiatum. In addition, there was a phase-locking relationship between neuronal spikes and the θ rhythms. However, HFS trains significantly decreased the phase-locking values between the spikes of pyramidal cells and the θ rhythms in stratum radiatum from 0.36 ± 0.12 to 0.06 ± 0.04 ( P < 0.001, paired t-test, N = 8). The phase-locking values of interneuron spikes were also decreased significantly from 0.27 ± 0.08 to 0.09 ± 0.05 ( P < 0.01, paired t-test, N = 8). Similar changes were obtained in the phase-locking values between neuronal spikes and the θ rhythms in the pyramidal layer. These results suggested that axonal HFS could eliminate the phase-locking relationship between action potentials of neurons and θ rhythms thereby changing the rhythmic firing of downstream neurons. HFS induced conduction block in the axons might be one of the underlying mechanisms. The finding is important for further understanding the mechanisms of DBS.

Analysis of the Responsiveness of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in the Treatment of OAG/OHT Patients.

AIM: Within the clinical setting, some patients have been identified as lacking in response to PGAs. This meta-analysis study aimed to evaluate the responsiveness of latanoprost, travoprost, bimatoprost, and tafluprost in OAG/OHT patients, latanoprost nonresponders (LNRs), and the IOP-reducing efficacy and safety. METHODS: A literature search was conducted on PubMed, Embase, and the Cochrane Controlled Trials Register. The primary clinical endpoint was the number of responders at the end of the study. The secondary clinical endpoint was the IOP reduction at the endpoint from baseline. Safety evaluation included five common adverse events: conjunctival hyperemia, hypertrichosis, ocular burning, ocular itching, and foreign-body sensation. RESULTS: Eleven articles containing ten RCTs were included in this meta-analysis study. The results highlighted that, in the OAG/OHT population, there was no statistically significant difference in the responsiveness of the four PGAs. Bimatoprost had a better IOP-reducing efficacy than latanoprost. There was no significant difference in the IOP-reducing efficacy of travoprost, latanoprost, and tafluprost. In LNRs, the responsiveness of bimatoprost, travoprost, and latanoprost did not show statistical differences. Bimatoprost reduced IOP with a greater extent than latanoprost and travoprost in LNRs, while there was no significant difference in the IOP-reducing efficacy of travoprost and latanoprost. No serious adverse events occurred with the treatment of the four PGAs. The prevalence of conjunctival hyperemia due to bimatoprost or tafluprost was significantly higher than that of latanoprost. Other adverse events had no significant difference between the four drugs. CONCLUSION: The existing studies cannot prove that latanoprost, travoprost, bimatoprost, and tafluprost have different responsiveness in OAG/OHT patients. Switching to bimatoprost or travoprost cannot achieve a significant improvement in responsiveness in LNRs. Bimatoprost has a better IOP-reducing efficacy than latanoprost and travoprost. No serious adverse events occurred during treatment with any medication we studied.

Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress.

Age-related eye diseases, including cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are the leading causes of vision loss in the world. Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye. The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body. This pathway is also active in the development of age-related eye diseases. A variety of drugs have been shown to treat age-related eye diseases through the Keap1-Nrf2-ARE (Kelch-like ECH-Associating protein 1- nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway. This review describes the role of oxidative stress in the development of age-related eye diseases, the function and regulation of the Keap1-Nrf2-ARE pathway, and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.

Novel Stimulation Paradigms with Temporally-Varying Parameters to Reduce Synchronous Activity at the Onset of High Frequency Stimulation in Rat Hippocampus.

Deep brain stimulation (DBS) has shown wide applications for treating various disorders in the central nervous system by using high frequency stimulation (HFS) sequences of electrical pulses. However, upon the onset of HFS sequences, the narrow pulses could induce synchronous firing of action potentials among large populations of neurons and cause a transient phase of "onset response" that is different from the subsequent steady state. To investigate the transient onset phase, the antidromically-evoked population spikes (APS) were used as an electrophysiological marker to evaluate the synchronous neuronal reactions to axonal HFS in the hippocampal CA1 region of anesthetized rats. New stimulation paradigms with time-varying intensity and frequency were developed to suppress the "onset responses". Results show that HFS paradigms with ramp-up intensity at the onset phase could suppress large APS potentials. In addition, an intensity ramp with a slower ramp-up rate or with a higher pulse frequency had greater suppression on APS amplitudes. Therefore, to reach a desired pulse intensity rapidly, a stimulation paradigm combining elevated frequency and ramp-up intensity was used to shorten the transition phase of initial HFS without evoking large APS potentials. The results of the study provide important clues for certain transient side effects of DBS and for development of new adaptive stimulation paradigms.

High frequency stimulation of afferent fibers generates asynchronous firing in the downstream neurons in hippocampus through partial block of axonal conduction.

Deep brain stimulation (DBS) is effective for treating neurological disorders in clinic. However, the therapeutic mechanisms of high-frequency stimulation (HFS) of DBS have not yet been elucidated. Previous studies have suggested that HFS-induced changes in axon conduction could have important contributions to the DBS effects and desiderate further studies. To investigate the effects of prolonged HFS of afferent axons on the firing of downstream neurons, HFS trains of 100 and 200Hz were applied on the Schaffer collaterals of the hippocampal CA1 region in anaesthetized rats. Single unit activity of putative pyramidal cells and interneurons in the downstream region was analyzed during the late periods of prolonged HFS when the axonal conduction was blocked. The results show that the firing rates of both pyramidal cells and interneurons increased rather than decreased during the period of axon block. However, the firing rates were far smaller than the stimulation frequency of HFS. In addition, the firing pattern of pyramidal cells changed from typical bursts during baseline recordings into regular single spikes during HFS periods. Furthermore, the HFS produced asynchronous firing in the downstream neurons in contrast to the synchronous firing induced by single pulses. Presumably, the HFS-induced block of axonal conduction was not complete. During the period of partial block, individual axons could recover intermittently and independently, and drive the downstream neurons to fire in an asynchronous pattern. This axonal mechanism of HFS provides a novel explanation for how DBS could replace an original pattern of neuronal activity by a HFS-modulated asynchronous firing in the target region thereby generating the therapeutic effects of DBS.