Femtosecond pulse generation from a SESAM mode-locked Tm,Ho:SrF2 laser at 2.08 µm.

We report on a passively mode-locked Tm,Ho:SrF2 laser employing a SESAM as saturable absorber (SA), delivering nearly Fourier-transform-limited 246 fs pulses at 2084nm without any additional intra- or extra-cavity dispersion compensation elements. This represents, to the best of our knowledge, the shortest pulses generated from the mode-locked fluoride bulk lasers in the 2-µm spectral range. Such compact femtosecond laser can be a potential seed source for large-sized fluoride bulk amplifier systems with exact gain match, enabling the generation of ultrashort intense pulses around 2 µm.

Tunable and mode-locked Tm,Ho:GdScO3 laser.

A novel, to the best of our knowledge, Tm,Ho:GdScO3 crystal grown using the Czochralski method was investigated for its polarized spectroscopic properties and laser performance in both tunable continuous-wave (CW) and mode-locked regimes. The crystal's multisite structure (Gd3+/Sc3+ site) and Tm3+/Ho3+ dopants contributed to spectral broadening, enabling a tunable laser operation from 1914 to 2125 nm (with a broad range of 215 nm). Additionally, a pulse duration of 72 fs was achieved for E || b polarization. These results demonstrate the potential of the Tm,Ho:GdScO3 perovskite crystal as a promising gain material for ultrafast lasers operating around 2 µm.

Implementation of personalized multidisciplinary neuropathy management program for chemotherapy-induced peripheral neuropathy symptoms in breast cancer patients.

OBJECTIVE: To construct a personalized multidisciplinary neurotoxicity management program for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in breast cancer patients and evaluate its application effects. METHODS: A retrospective analysis was conducted on clinical data of 133 breast cancer chemotherapy patients admitted to our hospital from January 2022 to January 2024. Based on the nursing protocols received, patients were divided into a control group (n = 66) and an intervention group (n = 67). The control group received conventional nursing interventions, while the intervention group received personalized nursing interventions in addition to the control group interventions. The nursing programs were carried out during chemotherapy. A comparison was made between the two groups before chemotherapy and 3 months after chemotherapy in terms of the degree of neuropathy, cancer-related fatigue, negative emotional status, and symptom management knowledge, attitudes, and practices (KAP). RESULTS: The intervention group showed significantly lower neuropathy severity (FACT/GOG-Ntx), cancer-related fatigue (CFS), and negative emotions (PHQ-9, GAD-7) scores after chemotherapy compared to the control group (p < 0.05). Additionally, the intervention group exhibited higher scores for symptom management knowledge, beliefs, and behaviors (p < 0.05). CONCLUSION: Personalized multidisciplinary neurotoxicity management program significantly improved neuropathy severity, reduced cancer-related fatigue and negative emotions, and enhanced symptom management knowledge, attitudes, and practices among breast cancer patients undergoing chemotherapy.

Efficient continuous wave and passively Q switched Er:GdScO3 laser using Fe:ZnSe at 2.8 µm.

We report on diode-pumped continuous wave and passively Q switched Er:GdScO3 crystal lasers at around 2.8 µm. A continuous wave output power of 579 mW was obtained with a slope efficiency of 16.6%. Using Fe:ZnSe as a saturable absorber, a passively Q switched laser operation was realized. A maximum output power of 32 mW was generated with the shortest pulse duration of 286 ns at a repetition rate of 157.3 kHz, leading to a pulse energy of 204 nJ and a pulse peak power of 0.7 W.

Efficient continuous wave and broad tunable lasers with the Tm:GdScO3 crystal.

The spectroscopic properties and tunable laser performances of the orthorhombic perovskite Tm:GdScO3 crystal grown by the Czochralski method are comparatively studied for polarization along different crystallographic axes. The polarized emission spectrum of Tm:GdScO3 along the b-axis exhibits, to the best of our knowledge, the broadest bandwidth among all the single Tm3+-doped bulk gain media, indicating the strong inhomogeneous line broadening of Tm3+ ions in GdScO3 and thus leads to a broad and smooth gain spectrum. Tunable laser operation with a tuning range as broad as 321 nm from 1824 nm to 2145 nm is achieved, which indicates its potential for few-optical-cycle pulse generation in the 2-µm spectral range.

Mode-locking of a Tm,Ho:CALYGO laser delivering 50 fs pulses at 2.08 µm.

We study the polarization-dependent laser performance of a novel, to the best of our knowledge, "mixed" Tm,Ho:CaYGdAlO4 crystal in the continuous-wave (CW) and mode-locked regimes. Both in terms of the CW tunability range (261 nm) and the minimum pulse duration (50 fs at 2078 nm, spectral width of 95 nm) in the mode-locked regime, σ-polarization is superior. With extended inhomogeneous spectral broadening due to structural and compositional disorder, Tm,Ho:CaYGdAlO4 is promising for few-optical-cycle pulse generation around 2 µm.

44-fs pulse generation at 2.05 µm from a SESAM mode-locked Tm:GdScO3 laser.

Pulses as short as 44 fs (6 optical cycles) with a spectral width of 120 nm are generated from a mode-locked solid-state laser near 2 µm employing an orthorhombic Tm:GdScO3 perovskite crystal. The average power amounts to 188 mW at a repetition rate of ∼77.6 MHz. The strong inhomogeneous line broadening in GdScO3 suggests optimum conditions for few-optical-cycle pulse generation of rare-earth ion doped GdScO3 bulk lasers.

A patient with acute myocardial infarction with acute lower extremity arterial embolization underwent amputation under general anesthesia.

INTRODUCTION: Acute peripheral and coronary artery embolism are common complications of diabetes mellitus and greatly affect the clinical outcome of patients with diabetes; however, there are few reports about the symptoms and prognosis of patients with acute myocardial infarction (AMI) and concurrent acute lower extremity arterial embolism (ALEAE). CASE PRESENTATION: A 44-year-old man with a history of 4 years of type 1 diabetes was admitted to hospital after suddenly experiencing severe pain in his right lower limb and feeling tightness in the left anterior chest area. Ultrasonography revealed distal occlusion of the right superficial femoral artery, and an electrocardiogram showed acute anterior interstitial myocardial infarction. After conservative treatment for 2 days, the patient had severe necrosis of the lower limbs and secondary injury of multiple organs. Haemodialysis and heparin anticoagulant therapy were performed before amputation. Twelve days after the operation, the patient's condition was stable, and he was transferred out of the intensive care unit. CONCLUSIONS: If patients with ALEAE miss the opportunity for early treatment, even with AMI, emergency amputation under general anaesthesia is the right strategy to save lives.

63 W wing-pumped Tm:YAG single-crystal fiber laser.

We present a high-power continuous-wave (CW) Tm:YAG single-crystal fiber (SCF) laser wing-pumped by laser diodes at 791 nm. A maximum output power of 63.3 W is achieved at ∼ 2.01 µm, corresponding to a slope efficiency of 34.2%. This is, to the best of our knowledge, the highest power obtained from the SCF laser in the 2 µm spectral range. In addition to the wing pumping scheme, the large surface-to-volume ratio of such fiber-geometry crystalline rod with diffusion-bonded undoped YAG end caps are benefited for the spatial uniform distribution of pump intensity and thermal load, and thus improving the power scalability.

Ho:LuAG single crystal fiber: growth, spectroscopy and laser characteristics.

Lutetium aluminum garnet single-crystal fiber (SCF, ∼ Φ 0.9 mm - 165 mm) doped with 0.5 at.% Ho3+ has been grown by the micro-pulling-down (µ-PD) technique. The room-temperature absorption and emission spectra exhibit similar features to the bulk crystal. Laser performances of the SCFs with two different pump configurations, i.e., pump guiding and free-space propagation, are studied by employing a 1.9-µm laser diode and a high-brightness fiber laser, respectively. Laser slope efficiencies obtained with both pump configurations can be higher than 50%, and a maximum output power of 6.01 W is achieved at ∼ 2.09 µm with the former pump. The comparable efficiency to the high-brightness pump is an indication of that high laser performance can also be expected through pump-guiding in the SCF even with a low pump beam quality.

Incorporation of a FRET Pair into a Riboswitch RNA to Measure Mg2+ Concentration and RNA Conformational Change in Cell.

Riboswitches are natural biosensors that can regulate gene expression by sensing small molecules. Knowledge of the structural dynamics of riboswitches is crucial to elucidate their regulatory mechanism and develop RNA biosensors. In this work, we incorporated the fluorophore, Cy3, and its quencher, TQ3, into a full-length adenine riboswitch RNA and its isolated aptamer domain to monitor the dynamics of the RNAs in vitro and in cell. The adenine riboswitch was sensitive to Mg2+ concentrations and could be used as a biosensor to measure cellular Mg2+ concentrations. Additionally, the TQ3/Cy3-labeled adenine riboswitch yielded a Mg2+ concentration that was similar to that measured using a commercial assay kit. Furthermore, the fluorescence response to the adenine of the TQ3/Cy3-labeled riboswitch RNA was applied to determine the proportions of multiple RNA conformational changes in cells. The strategy developed in this work can be used to probe the dynamics of other RNAs in cells and may facilitate the developments of RNA biosensors, drugs and engineering.

Tm:YAG single-crystal fiber laser.

In this Letter, to the best of our knowledge, we present the first thulium (Tm) single-crystal fiber (SCF) laser with free-space propagation of the laser beam only. The SCF is equipped with diffusion-bonded end caps of undoped YAG for better thermal management and enhancement of pump guiding. By utilizing mode matching and pump guiding in different SCF parts, an output power of 9.1 W is achieved at ∼2.02µm with a slope efficiency of 49.4%. This straightforward approach, which is also simple to realize and is based on combining the advantages of fiber-geometry structure and crystalline properties of Tm:YAG, is expected to be useful for 2 µm amplification stages in different time formats as well.

Morvan syndrome associated with LGI1 antibody: a case report.

BACKGROUND: Morvan syndrome (MoS) is a rare autoimmune syndrome associated with antibodies against two kinds of potassium channel proteins, contactin associated protein-like 2 (CASPR2) and leucine-rich glioma inactivated protein 1 (LGI1). MoS patients with only LGI1-antibody seropositivity have rarely been reported. Here, we describe a 64-year-old male MoS patient with only LGI1-antibody seropositivity. CASE PRESENTATION: A 64-year-old male patient was referred to our hospital due to limb pain, widespread myokymia, insomnia, constipation, and hyperhidrosis for 1 month. The patient was diagnosed with MoS based on the clinical symptoms and positive LGI1-antibody in serum. He was treated with intravenous immunoglobulin (IVIG), intravenous methylprednisolone followed by oral prednisone, and other drugs for symptomatic relief. Several days later, myokymia and insomnia symptoms improved. After 60 days of follow-up, all the drugs had been stopped for 2 weeks, and the patient achieved complete remission without any medical side effects. CONCLUSION: We report the clinical characteristics of a Chinese MoS patient with only LGI1-antibody seropositivity, and further support the view that non-neoplasm MoS patients respond well to immunotherapy.

A de novo variant of POLR3B causes demyelinating Charcot-Marie-Tooth disease in a Chinese patient: a case report.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants. CASE PRESENTATION: A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A). CONCLUSIONS: In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.

The proteasome activator REGγ counteracts immunoproteasome expression and autoimmunity.

For quite a long time, the 11S proteasome activator REGɑ and REGß, but not REGγ, are known to control immunoproteasome and promote antigen processing. Here, we demonstrate that REGγ functions as an inhibitor for immunoproteasome and autoimmune disease. Depletion of REGγ promotes MHC class I-restricted presentation to prime CD8+ T cells in vitro and in vivo. Mice deficient for REGγ have elevation of CD8+ T cells and DCs, and develop age-related spontaneous autoimmune symptoms. Mechanistically, REGγ specifically interacts with phosphorylated STAT3 and promotes its degradation in vitro and in cells. Inhibition of STAT3 dramatically attenuates levels of LMP2/LMP7 and antigen presentation in cells lacking REGγ. Importantly, treatment with STAT3 or LMP2/7 inhibitor prevented accumulation of immune complex in REGγ-/- kidney. Moreover, REGγ-/- mice also expedites Pristane-induced lupus. Bioinformatics and immunohistological analyses of clinical samples have correlated lower expression of REGγ with enhanced expression of phosphorylated STAT3, LMP2 and LMP7 in human Lupus Nephritis. Collectively, our results support the concept that REGγ is a new regulator of immunoproteasome to balance autoimmunity.

Ultrasound-Guided Cervical Nerve Root Block for the Treatment of Acute Cervical Herpes Zoster: A Randomized Controlled Clinical Study.

OBJECTIVES: To evaluate the efficacy and safety of ultrasound-guided cervical nerve root block (CRB) on acute pain and its preventive effects on post-herpetic neuralgia (PHN) in patients with cervical herpes zoster (HZ). METHODS: 140 recruited participants were randomized 1:1 to receive ultrasound-guided CRB with either mixed drug liquid (treatment group) or similar looking placebo (placebo group). All patients received a 7-day course of oral antiviral treatment, pregabalin, and analgesics as needed. The primary efficacy was assessed on the basis of HZ burden of illness (HZ-BOI) scores over 30 days (BOI-30AUC ). Secondary outcomes included HZ-BOI scores through 30 to 90 days (BOI-30-90AUC ) and 90 to 180 days (BOI-90-180AUC ), quality of life (QoL) outcomes, concomitant analgesic consumption, and the incidence of PHN. Adverse events were recorded to evaluate safety. RESULTS: The BOI-30AUC values were 92.55 and 112.72 for the treatment and placebo groups, respectively (P < 0.01). Both the BOI-30-90AUC and BOI-90-180AUC in the treatment group were lower than those in the placebo group (P < 0.01). The incidence of PHN at 90 days was significantly less than that at 180 days in the treatment group (P = 0.036). A better improvement in QoL was found in the treatment group (P < 0.05). There was a greater decrease in analgesic use in the treatment group as compared to the placebo group (P < 0.05). No serious adverse events were observed. CONCLUSIONS: Ultrasound-guided CRB represented an early intervention and preventive strategy to reduce the BOI due to acute HZ in the cervical dermatome region, and might be feasible to reduce the incidence of PHN.

Hybrid Membrane-Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease.

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.

Alzheimer's disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling.

Amyloid-ß, tau pathology, and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease (AD). However, these proteins represent only a fraction of the complex biological processes underlying AD, and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers. More AD-specific early diagnostic and disease staging biomarkers are needed. In this study, we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid (CSF) and serum samples in a discovery cohort comprising 98 participants. Candidate biomarkers were validated by parallel reaction monitoring-based targeted proteomic assays in an independent multicenter cohort comprising 288 participants. We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort, identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers, respectively. In the validation cohort, 58 and 21 CSF proteins, as well as 12 and 18 serum proteins, were verified as early diagnostic and staging biomarkers, respectively. Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment (MCI) due to AD from normal cognition with areas under the curve of 0.984 and 0.881, respectively. The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases. Moreover, we identified 21 CSF and 18 serum stage-associated proteins reflecting AD stages. Our findings provide a foundation for developing blood-based tests for AD screening and staging in clinical practice.

LncRNA HOTTIP promotes inflammatory response in acute gouty arthritis via miR-101-3p/BRD4 axis.

INTRODUCTION: Acute gouty arthritis (AGA) is characterized by the accumulation of pro-inflammatory factors. This research aimed to examine the regulation of long non-coding RNA HOXA distal transcript antisense RNA (HOTTIP) in AGA on inflammation and its potential mechanisms. METHODS: Serum levels of HOTTIP in AGA patients were examined by reverse-transcription quantitative polymerase chain reaction. The receiver operating characteristic curve was performed in the diagnosis of AGA patients. Monosodium urate (MSU) stimulation of THP-1-derived macrophages was used to establish an in vitro AGA model. Enzyme-linked immunosorbent assay was carried out to assess the levels of pro-inflammatory cytokines. Pearson correlation was applied to examine the correlation. RNA immunoprecipitation assay and dual-luciferase reporter assay were employed to identify the targeting relationship between miR-101-3p and HOTTIP or bromodomain-containing 4 (BRD4). RESULTS: HOTTIP and BRD4 were statistically overexpressed in AGA patients compared with controls, while miR-101-3p was reduced (P < 0.05). Serum HOTTIP can significantly distinguish AGA patients from healthy controls. HOTTIP bound with miR-101-3p then augmented BRD4 via a competing endogenous RNA mechanism. Additionally, HOTTIP levels were elevated in a dose-dependent manner by MSU (P < 0.05). Weakened HOTTIP significantly inhibited MSU-induced release of pro-inflammatory factors interleukin (IL)-1ß, IL-8, and transforming growth factor-α in macrophages (P < 0.05), but this inhibition was reversed by silencing miR-101-3p (P < 0.05). CONCLUSION: In short, HOTTIP contributes to inflammation via miR-101-3p/BRD4 axis, and serves as a new diagnostic biomarker. This study offers a renewed perspective on the diagnosis and treatment of AGA.

Observation of structural switch in nascent SAM-VI riboswitch during transcription at single-nucleotide and single-molecule resolution.

Growing RNAs fold differently as they are transcribed, which modulates their finally adopted structures. Riboswitches regulate gene expression by structural change, which are sensitive to co-transcriptionally structural biology. Here we develop a strategy to track the structural change of RNAs during transcription at single-nucleotide and single-molecule resolution and use it to monitor individual transcripts of the SAM-VI riboswitch (riboSAM) as transcription proceeds, observing co-existence of five states in riboSAM. We report a bifurcated helix in one newly identified state from NMR and single-molecule FRET (smFRET) results, and its presence directs the translation inhibition in our cellular translation experiments. A model is proposed to illustrate the distinct switch patterns and gene-regulatory outcome of riboSAM when SAM is present or absent. Our strategy enables the precise mapping of RNAs' conformational landscape during transcription, and may combine with detection methods other than smFRET for structural studies of RNAs in general.