A BCG kill switch strain protects against Mycobacterium tuberculosis in mice and non-human primates with improved safety and immunogenicity.

Improved vaccination strategies for tuberculosis are needed. Intravenous (i.v.

Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.

Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim.

[Buyang Huanwu Decoction attenuates cerebral ischemia-reperfusion injury in rats via miR-26a-5p mediated PTEN/PI3K/Akt signaling pathway].

This study aims to investigate the mechanism of Buyang Huanwu Decoction in treatment of cerebral ischemia-reperfusion injury in rats. A total of 180 SD rats were randomly divided into 5 different groups: sham group, model group, Buyang Huanwu Decoction group, Buyang Huanwu Decoction + miR-26a-5p agomir(agomir) group, Buyang Huanwu Decoction + miR-26a-5p agomir negative control(agomir NC) group. There were 36 rats in each group.

Dual beam optical coherence tomography angiography for decoupling axial velocity gradient.

Axial velocity gradient (AVG) in the optical coherence tomography angiography (OCTA) signal affects measurement accuracy when the flow is not perpendicular to the scanning beam. We developed a dual beam OCTA method to decouple the contribution of AVG from the decorrelation signal. Decoupling is first verified by phantom experiments which reduces measurement uncertainty from 1.

The effect of salidroside in promoting endogenous neural regeneration after cerebral ischemia/reperfusion involves notch signaling pathway and neurotrophic factors.

Background: Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown.

Comparison of the repeatability and reproducibility of corneal thickness mapping using optical coherence tomography according to tear film break-up time.

Background: To compare the repeatability and reproducibility of corneal and corneal epithelial thickness mapping using anterior segment optical coherence tomography (AS-OCT) according to tear film break-up time (TBUT).

Methods: The included eyes were divided into three subgroups according to TBUT (group 1: TBUT ≤ 5 s, group 2: 5 s < TBUT ≤ 10 s, and group 3: TBUT > 10 s). All eyes were imaged separately thrice by two operators to obtain the thickness maps (TMs) of the cornea and corneal epithelium based on spatial zones encompassing a 9-mm-diameter area.

Coaxial Bright and Dark Field Optical Coherence Tomography.

To improve the signal collection efficiency of Optical Coherence Tomography (OCT) for biomedical applications. A novel coaxial optical design was implemented, utilizing a wavefront-division beam splitter in the sample arm with a 45-degree rod mirror. This design allowed for the simultaneous collection of bright and dark field signals.

Development of an Engineered Strain for a Safe and Effective Tuberculosis Human Challenge Model.

Human challenge experiments could greatly accelerate the development of a tuberculosis (TB) vaccine. Human challenge for tuberculosis requires a strain that can both replicate in the host and be reliably cleared. To accomplish this, we designed (Mtb) strains featuring up to three orthogonal kill switches, tightly regulated by exogenous tetracyclines and trimethoprim.

Development of a two-beveled-fiber polarized fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy.

We report on the development of a two-beveled-fiber polarized (TBFP) fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy. The two-beveled fibers positioned symmetrically along a ball lens, in synergy with paired parallel-polarized polarizers integrated between the fibers and the ball lens, maximize the Raman signal excitation and collection from the superficial epithelium where gastrointestinal (GI) precancer arises. Monte Carlo (MC) simulations and two-layer tissue phantom experiments show that the probe developed detects ∼90% of the Raman signal from the superficial epithelium.

Real-time in vivo cancer staging of nasopharyngeal carcinoma patients with rapid fiberoptic Raman endoscopy.

Cancer staging is important to guide treatment and for prognostication. This work aims to demonstrate the ability of rapid fiberoptic Raman endoscopy for real-time in vivo cancer staging of nasopharyngeal cancer (NPC) patients. We interrogate 278 tissue sites on the primary NPC with different cancer stages from 61 NPC patients and 50 healthy volunteers using rapid fiberoptic Raman endoscopy examination.

Should patients with epilepsy be vaccinated against coronavirus disease 2019? A systematic review and meta-analysis.

Objective: The coronavirus disease 2019 (COVID-19) vaccination coverage, willingness, and safety profiles in patients with epilepsy remain poorly understood. We aimed to summarize the available evidence of COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy.

Methods: We performed a literature search in the Pubmed, EMBASE, and Cochrane Central Register database between 1 January 2020 and 30 April 2022.

Optical coherence tomography-guided confocal Raman microspectroscopy for rapid measurements in tissues.

We report a joint system with both confocal Raman spectroscopy (CRS) and optical coherence tomography (OCT) modules capable of quickly addressing the region of interest in a tissue for targeted Raman measurements from OCT. By using an electrically tunable lens in the Raman module, the focus of the module can be adjusted to address any specific depth indicated in an OCT image in a few milliseconds. We demonstrate the performance of the joint system in the depth dependent measurements of an swine tissue and human skin.

Deep Learning-Guided Fiberoptic Raman Spectroscopy Enables Real-Time Diagnosis and Assessment of Nasopharyngeal Carcinoma and Post-treatment Efficacy during Endoscopy.

In this work, we develop a deep learning-guided fiberoptic Raman diagnostic platform to assess its ability of real-time nasopharyngeal carcinoma (NPC) diagnosis and post-treatment follow-up of NPC patients. The robust Raman diagnostic platform is established using innovative multi-layer Raman-specified convolutional neural networks (RS-CNN) together with simultaneous fingerprint and high-wavenumber spectra acquired within sub-seconds using a fiberoptic Raman endoscopy system. We have acquired a total of 15,354 FP/HW Raman spectra (control: 1761; NPC: 4147; and post-treatment (PT): 9446) from 888 tissue sites of 418 subjects (healthy control: 85; NPC: 82; and PT: 251) during endoscopic examination.

Genetic models of latent tuberculosis in mice reveal differential influence of adaptive immunity.

Studying latent Mycobacterium tuberculosis (Mtb) infection has been limited by the lack of a suitable mouse model. We discovered that transient depletion of biotin protein ligase (BPL) and thioredoxin reductase (TrxB2) results in latent infections during which Mtb cannot be detected but that relapse in a subset of mice. The immune requirements for Mtb control during latency, and the frequency of relapse, were strikingly different depending on how latency was established.

Corneal Vertical and Horizontal Thickness Profiles Generated by UHR-OCT for Suspected and Subclinical Keratoconus Diagnosis.

Purpose: To verify the diagnostic power of vertical and horizontal thickness profiles of the corneal sublayers generated by ultra-high resolution optical coherence tomography (UHROCT) in subclinical and suspected keratoconus.

Methods: In this cross-sectional study, 25 eyes with confirmed keratoconus, 63 eyes with suspected keratoconus, 15 eyes with subclinical keratoconus, and 42 normal eyes were investigated. Vertical and horizontal thickness profiles of the corneal epithelium, Bowman's layer, and stroma were measured by UHR-OCT.

Relationship between corneal biomechanical parameters and corneal sublayer thickness measured by Corvis ST and UHR-OCT in keratoconus and normal eyes.

Background: To explore the relationship between corneal biomechanical parameters and corneal sublayer thickness using corneal visualization Scheimpflug technology (Corvis ST) and ultrahigh-resolution optical coherence tomography (UHR-OCT) in clinical and suspected keratoconus and normal eyes.

Methods: Cross-sectional prospective study. A total of 94 eyes of 70 participants were recruited.

Label-Free Follow-Up Surveying of Post-Treatment Efficacy and Recurrence in Nasopharyngeal Carcinoma Patients with Fiberoptic Raman Endoscopy.

Recurrent nasopharyngeal carcinoma (NPC) is the main cause of poor prognosis for NPC patients after chemo- and radiotherapies. Subsequent long-term follow-ups of post-treatment patients are crucial for the early discovery of tumor recurrence with timely intervention. Current clinical imaging methods based on tissue morphology encounter difficulties in differentiating recurrent tumors from post-treatment inflammation and fibrosis.

Fiber-Optic Raman Spectroscopy with Nature-Inspired Genetic Algorithms Enhances Real-Time in Vivo Detection and Diagnosis of Nasopharyngeal Carcinoma.

Raman spectroscopy is an optical vibrational spectroscopic technique capable of probing specific biochemical structures and conformation of tissue and cells in biomedical systems. This work aims to assess the clinical utility of a fiber-optic Raman spectroscopy with nature-inspired genetic algorithms for enhancing in vivo detection and diagnosis of nasopharyngeal carcinoma (NPC) patients. The Raman diagnostic platform is developed based on simultaneous fingerprint (FP) and high-wavenumber (HW) fiber-optic Raman endoscopy associated with genetic algorithms-partial least-squares-linear discriminant analysis (GA-PLS-LDA).

Effect of baicalin on renal function in patients with diabetic nephropathy and its therapeutic mechanism.

The present study observed the effect of baicalin on blood glucose and renal function in patients with diabetic nephropathy and explored its mechanism of action. A total of 95 patients diagnosed with diabetic nephropathy by clinical and laboratory examinations were selected and randomly divided into a control and treatment group. The control group included 45 patients who were treated with routine symptomatic treatment.

Epi-Detected Hyperspectral Stimulated Raman Scattering Microscopy for Label-Free Molecular Subtyping of Glioblastomas.

We report the development and implementation of an epi-detected spectral-focusing hyperspectral stimulated Raman scattering (SRS) imaging technique for label-free biomolecular subtyping of glioblastomas (GBMs). The hyperspectral SRS imaging technique developed generates SRS image stacks (from 2800 to 3020 cm at 7 cm intervals) within 30 s through controlling the time delay between the chirped pump and Stokes beams. SRS images at representative Raman shifts (e.

Rab5, Rab7, and Rab11 Are Required for Caveola-Dependent Endocytosis of Classical Swine Fever Virus in Porcine Alveolar Macrophages.

The members of utilize several endocytic pathways to enter a variety of host cells. Our previous work showed that classical swine fever virus (CSFV) enters porcine kidney (PK-15) cells through a clathrin-dependent pathway that requires Rab5 and Rab7. The entry mechanism for CSFV into other cell lines remains unclear, for instance, porcine alveolar macrophages (3D4/21 cells).

Porcine Mx1 Protein Inhibits Classical Swine Fever Virus Replication by Targeting Nonstructural Protein NS5B.

Mx proteins are interferon (IFN)-induced GTPases that have broad antiviral activity against a wide range of RNA and DNA viruses; they belong to the dynamin superfamily of large GTPases. In this study, we confirmed the anti-classical swine fever virus (CSFV) activity of porcine Mx1 and showed that porcine Mx2 (poMx2), human MxA (huMxA), and mouse Mx1 (mmMx1) also have anti-CSFV activity Small interfering RNA (siRNA) experiments revealed that depletion of endogenous poMx1 or poMx2 enhanced CSFV replication, suggesting that porcine Mx proteins are responsible for the antiviral activity of interferon alpha (IFN-α) against CSFV infection. Confocal microscopy, immunoprecipitation, glutathione -transferase (GST) pulldown, and bimolecular fluorescence complementation (BiFC) demonstrated that poMx1 associated with NS5B, the RNA-dependent RNA polymerase (RdRp) of CSFV.