Toward a Mechanistic Understanding of Bacterial Rod Shape Formation and Regulation.

One of the most common bacterial shapes is a rod, yet we have a limited understanding of how this simple shape is constructed. While only six proteins are required for rod shape, we are just beginning to understand how they self-organize to build the micron-sized enveloping structures that define bacterial shape out of nanometer-sized glycan strains. Here, we detail and summarize the insights gained over the last 20 years into this complex problem that have been achieved with a wide variety of different approaches. We also explain and compare both current and past models of rod shape formation and maintenance and then highlight recent insights into how the Rod complex might be regulated.

Restoration of thoracic kyphosis in adolescent idiopathic scoliosis with patient-specific rods: did the preoperative plan match postoperative sagittal alignment?

PURPOSE: To determine if the planned sagittal profile for thoracic kyphosis (TK) restoration was achieved after adolescent idiopathic scoliosis (AIS) surgery using a novel hybrid construct with apical double bands and precontoured patient-specific rods (PSR) made according to the detailed surgical plan for the desired sagittal plane. METHODS: AIS patients with a Lenke type 1-4 primary right thoracic curve who underwent corrective surgery by a single surgeon and had minimum 24-month follow-up were analyzed retrospectively from a prospective database. All patients underwent simultaneous translation on two rods with apical double bands and PSR. Clinical outcomes in terms of sagittal 2D TK (T4-T12), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL mismatch, rod angle, and rod deflection were compared between preoperative, planned, and 24-month data, while 3D apical rotation, 3D TK (T5-T12), sagittal thoracolumbar angle, degree of curvature at L1-L4 and L4-S1, proximal junctional angle, and distal junctional angle were compared at baseline and at 6 and 24 months postoperatively. SRS-22 questionnaire scores were obtained at baseline and 24 months postoperatively. RESULTS: Forty-eight patients were included. Study patients had a median coronal thoracic curve of 62.7° preoperatively and 22.4° at 24-month follow-up (p < 0.001). Median TK gain was 6.5° for the entire cohort (n = 48) and 19.1° in the Lenke type 1 and 2 hypokyphotic subgroup (n = 14). Both groups had no significant changes between planned and 24-month TK (p = 0.068 and p = 0.943, respectively), rod angle (p = 0.776 and p = 0.548, respectively), or rod deflection (p = 0.661 and p = 0.850, respectively). For the overall study cohort, median LL gain was 7.0° (p < 0.001), 3D apical derotation was 10.7° (p < 0.001), and change in 3D TK was 36° (p < 0.001). No instance of proximal junctional kyphosis was observed. SRS-22 scores for pain, self-image, and satisfaction differed significantly between the preoperative and 24-month follow-up time-points. CONCLUSIONS: With sagittal plane planning, desired TK, improved reciprocal changes in LL, and minimal changes in rod shape can be achieved in patients with AIS.

GROWTH POLE RING protein forms a 200-nm-diameter ring structure essential for polar growth and rod shape in Agrobacterium tumefaciens.

Polar growth in Agrobacterium pirates and repurposes well-known bacterial cell cycle proteins, such as FtsZ, FtsA, PopZ, and PodJ. Here we identify a heretofore unknown protein that we name GROWTH POLE RING (GPR) due to its striking localization as a hexameric ring at the growth pole during polar growth. GPR also localizes at the midcell late in the cell cycle just before division, where it is then poised to be precisely localized at new growth poles in sibling cells. GPR is 2,115 aa long, with two N-terminal transmembrane domains placing the bulk of the protein in the cytoplasm, N- and C-terminal proline-rich disordered regions, and a large 1,700-aa central region of continuous α-helical domains. This latter region contains 12 predicted adjacent or overlapping apolipoprotein domains that may function to sequester lipids during polar growth. Stable genetic deletion or riboswitch-controlled depletion results in spherical cells that grow poorly; thus, GPR is essential for wild-type growth and morphology. As GPR has no predicted enzymatic domains and it forms a distinct 200-nm-diameter ring, we propose that GPR is a structural component of an organizing center for peptidoglycan and membrane syntheses critical for cell envelope formation during polar growth. GPR homologs are found in numerous Rhizobiales; thus, our results and proposed model are fundamental to understanding polar growth strategy in a variety of bacterial species.

Internal pressure-induced formation of hemispherical poles in Bacillus subtilis.

The cell of a rod-shaped bacterium is composed of a cylinder and two hemispherical poles. In recent decades, the molecular mechanism of morphogenesis in rod-shaped bacteria has received extensive research. However, most works have focused on the morphogenesis of cylinders, and the morphogenesis of the hemispherical poles remains unclear. In the past, the pole of bacterial cell wall was considered as a rigid hemispherical structure. However, our work indicated that the pole in the isolated sacculi from Bacillus subtilis was a flat structure instead of a hemisphere form. Further works showed that internal pressure was responsible for shaping the hemispherical poles, indicating an elastic nature of the cell wall in poles. In addition, we found that the internal pressure was able to transform septa into hemispherical shape which is similar to normal poles. Based on our work, we proposed a model for the internal pressure-induced formation of hemispherical poles in B. subtilis, and this work may provide new clues into basic knowledge of the morphogenesis of rod-shaped bacteria.

Spatial Structure Regulation: A Rod-Shaped Viologen Enables Long Lifetime in Aqueous Redox Flow Batteries.

A stable rod-like sulfonated viologen (R-Vi) derivative is developed through a spatial-structure-adjustment strategy for neutral aqueous organic redox flow batteries (AORFBs). The obtained R-Vi features four individual methyl groups on the 2,2',6,6'-positions of the 4,4'-bipyridine core ring. The tethered methyls confine the movement of the alkyl chain as well as the sulfonic anion, thus driving the spatial structure from sigmoid to rod shape. The R-Vi with weak charge attraction and large molecular dimension displays an ultralow membrane permeability that is only 14.7 % of that of typical sigmoid viologen. Moreover, the electron-donating effect of methyls endows R-Vi with the lowest redox potential of -0.55 V vs. SHE among one-electron-storage viologen-based AORFBs. The AORFB with the R-Vi anolyte and a K4 Fe(CN)6 catholyte exhibits an energy efficiency up to 87 % and extremely low capacity-fade rate of 0.007 % per cycle in 3200 continuous cycles.

The Influence of Nanoparticle Shape on Protein Corona Formation.

Nanoparticles have become an important utility in many areas of medical treatment such as targeted drug and treatment delivery as well as imaging and diagnostics. These advances require a complete understanding of nanoparticles' fate once placed in the body. Upon exposure to blood, proteins adsorb onto the nanoparticles surface and form a protein corona, which determines the particles' biological fate. This study reports on the protein corona formation from blood serum and plasma on spherical and rod-shaped nanoparticles. These two types of mesoporous silica nanoparticles have identical chemistry, porosity, surface potential, and size in the y-dimension, one being a sphere and the other a rod shape. The results show a significantly larger amount of protein attaching from both plasma and serum on the rod-like particles compared to the spheres. Interrogation of the protein corona by liquid chromatography-mass spectrometry reveals shape-dependent differences in the adsorption of immunoglobulins and albumin proteins from both plasma and serum. This study points to the need for taking nanoparticle shape into consideration because it can have a significant impact on the fate and therapeutic potential of nanoparticles when placed in the body.

Rod-shaped gold nanoparticles biosynthesized using Pb2+-induced fungus Aspergillus sp. WL-Au.

Gold nanoparticles (AuNPs) attracted much attention owing to their distinguished characteristics and applications. In this study, rod-shaped AuNPs were biosynthesized using Pb2+-induced fungus Aspergillus sp. The synthesized AuNPs showed a UV-vis absorption peak at 534 nm. Scanning electron microscopy and transmission electron microscopy analyses showed that rod-shaped AuNPs were biosynthesized and attached on the mycelia surfaces. Energy-dispersive spectrometer analysis identified gold as the unique metallic composition of synthesized nanoparticles. X-ray powder diffraction analysis showed that the AuNPs were face-centered cubic crystalline structure. Furthermore, Fourier transform infrared spectroscopy analysis detected functional groups, including C = O, C-O-C, amine I and II which played active roles in AuNPs formation. In addition, the main shape of synthesized AuNPs changed from sphere to rod-shape with the increase of biomass and Pb2+ concentration. This study reports quite uniform rod-shaped AuNPs biosynthesized using Pb2+-induced fungus Aspergillus sp. WL-Au for the first time. This will provide a valid alternative for oriented biosynthesis of AuNPs.

RodZ links MreB to cell wall synthesis to mediate MreB rotation and robust morphogenesis.

The rod shape of most bacteria requires the actin homolog, MreB. Whereas MreB was initially thought to statically define rod shape, recent studies found that MreB dynamically rotates around the cell circumference dependent on cell wall synthesis. However, the mechanism by which cytoplasmic MreB is linked to extracytoplasmic cell wall synthesis and the function of this linkage for morphogenesis has remained unclear. Here we demonstrate that the transmembrane protein RodZ mediates MreB rotation by directly or indirectly coupling MreB to cell wall synthesis enzymes. Furthermore, we map the RodZ domains that link MreB to cell wall synthesis and identify mreB mutants that suppress the shape defect of ΔrodZ without restoring rotation, uncoupling rotation from rod-like growth. Surprisingly, MreB rotation is dispensable for rod-like shape determination under standard laboratory conditions but is required for the robustness of rod shape and growth under conditions of cell wall stress.

A versatile papaya mosaic virus (PapMV) vaccine platform based on sortase-mediated antigen coupling.

BACKGROUND: Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide. This represents a serious limitation to the utility of this approach as fusion of small peptides only is tolerated. RESULTS: We have developed a novel approach in which peptides are fused directly to pre-formed PapMV nanoparticles. This approach is based on the use of a bacterial transpeptidase (sortase A; SrtA) that can attach the peptide directly to the nanoparticle. An engineered PapMV CP harbouring the SrtA recognition motif allows efficient coupling. To refine our engineering, and to predict the efficacy of coupling with SrtA, we modeled the PapMV structure based on the known structure of PapMV CP and on recent reports revealing the structure of two closely related potexviruses: pepino mosaic virus (PepMV) and bamboo mosaic virus (BaMV). We show that SrtA can allow the attachment of long peptides [Influenza M2e peptide (26 amino acids) and the HIV-1 T20 peptide (39 amino acids)] to PapMV nanoparticles. Consistent with our PapMV structural model, we show that around 30% of PapMV CP subunits in each nanoparticle can be fused to the peptide antigen. As predicted, engineered nanoparticles were capable of inducing a strong antibody response to the fused antigen. Finally, in a challenge study with influenza virus, we show that mice vaccinated with PapMV-M2e are protected from infection. CONCLUSIONS: This technology will allow the development of vaccines harbouring long peptides containing several B and/or T cell epitopes that can contribute to a broad and robust protection from infection. The design can be fast, versatile and can be adapted to the development of vaccines for many infectious diseases as well as cancer vaccines.

The Current Status of the Distribution Range of the Western Pine Beetle, Dendroctonus brevicomis (Curculionidae: Solytinae) in Northern Mexico.

The distribution range of the western pine beetle Dendroctonus brevicomis LeConte (Coleoptera: Curculionidae) is supported only by scattered records in the northern parts of Mexico, suggesting that its populations may be marginal and rare in this region. In this study, we review the geographical distribution of D. brevicomis in northern Mexico and perform a geometric morphometric analysis of seminal rod shape to evaluate its reliability for identifying this species with respect to other members of the Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae) complex. Our results provide 30 new records, with 26 distributed in the Sierra Madre Occidental and 4 in the Sierra Madre Oriental. These records extend the known distribution range of D. brevicomis to Durango and Tamaulipas states in northern Mexico. Furthermore, we find high geographic variation in size and shape of the seminal rod, with conspicous differences among individuals from different geographical regions, namely west and east of the Great Basin and between mountain systems in Mexico.

Low radius of curvature growth-friendly rib-based implants increase the risk of developing clinically significant proximal junctional kyphosis.

BACKGROUND: Clinically significant proximal junctional kyphosis (PJK) occurs in 20% of children with scoliosis treated with posterior distraction-based growth-friendly surgery. In an effort to identify modifiable risk factors, it has been theorized biomechanically that low radius of curvature (ROC) implants (i.e., more curved rods) may increase post-operative thoracic kyphosis, and thus may pose a higher risk of developing PJK. We sought to test the hypothesis that early onset scoliosis (EOS) patients treated with low ROC distraction-based implants will have a greater risk of developing clinically significant PJK as compared to those treated with high ROC (straighter) implants. METHODS: We conducted a retrospective review of prospectively collected data obtained from a multi-centre EOS database on children treated with rib-based distraction with a minimum 2-year follow-up. Variables of interest included: implant ROC at index (220 mm or 500 mm), participant age, pre-operative scoliosis, pre-operative kyphosis, and scoliosis etiology. PJK was defined as clinically significant if revision surgery with a superior extension of the upper instrumented vertebrae was performed. RESULTS: In 148 participants with scoliosis, there was a higher risk of clinically significant PJK with low ROC (more curved) rods (OR: 2.6 (95% CI 1.09-5.99), χ2 (1, n = 148) = 4.8, p = 0.03). Participants had a mean pre-operative age of 5.3 years (4.6y 220 mm vs 6.2y 500 mm, p = 0.002). A logistic regression model was created with age as a confounding variable, but it was determined to be not significant (p = 0.6). Scoliosis etiologies included 52 neuromuscular, 52 congenital, 27 idiopathic, 17 syndromic with no significant differences in PJK risk between etiologies (p = 0.07). Overall, participants had pre-op scoliosis of 69° (67° 220 mm vs 72° 500 mm, p = 0.2), and kyphosis of 48° (45° 220 mm vs 51° 500 mm, p = 0.1). The change in thoracic kyphosis pre-operatively to final follow-up (mean 4.0 ± 0.2 years) was higher in participants treated with 220 mm implants compared to 500 mm implants (220 mm: 7.5 ± 2.6° vs 500 mm: - 4.0 ± 3.0°, p = 0.004). CONCLUSIONS: Use of low ROC (more curved) posterior distraction implants is associated with a significantly greater increase in thoracic kyphosis which likely led to a higher risk of developing clinically significant PJK in participants with EOS. LEVEL OF EVIDENCE: Level III - retrospective comparative study.

Rod-shaped nintedanib nanocrystals improved oral bioavailability through multiple intestinal absorption pathways.

Nintedanib (BIBF) is a biopharmaceutical classification system II (BCS II) drug that has a good therapeutic effect for the treatment of nonsmall cell lung cancer; however, it shows poor oral bioavailability due to low dissolution and intestinal absorption. This study aims to fabricate rod-shaped nanocrystals to enhance oral bioavailability by improving the dissolution and absorption of BIBF in the intestine. By prescription screening, BIBF nanocrystals (BIBF-NCs) with a particle size of 325.30 ± 1.03 nm and zeta potential of 32.70 ± 1.24 mV were fabricated by an antisolvent precipitation-ultrasound approach with a stabilizer of sodium carboxyl methyl cellulose (CMC-Na). BIBF-NCs exhibited a rod-shaped morphology by transmission electron microscopy (TEM). The results of powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) showed that the crystal form of BIBF in BIBF-NCs was altered. The BIBF-NCs remarkably improved the saturation solubility and dissolution of BIBF compared with BIBF powder. According to the results of in situ single-pass intestinal perfusion (SPIP), BIBF-NCs showed improved absorption and membrane permeability, with Ka and Papp values in the jejunum of 0.21 ± 0.01 min-1 and (4.34 ± 0.11) × 10-4 cm/min, respectively. Further, the Ka and Papp values of BIBF-NCs were all reduced significantly after the addition of inhibitors colchicine, chlorpromazine and indomethacin, which demonstrated that BIBF-NCs could be absorbed by endocytosis mediated by caveolae and clathrin and micropinocytosis in the intestine. The cell evaluation results showed that BIBF-NCs could be taken up by macrophages and transported from Caco-2 monolayers. The in vivo pharmacokinetic results showed that the bioavailability of the BIBF-NCs was 2.51-fold higher than that of the BIBF solution (BIBF-Sol) after oral administration with a longer Tmax (4.50 ± 1.00 h vs. 2.60 ± 1.92 h). In summary, rod-shaped BIBF-NCs could significantly improve oral bioavailability through multiple intestinal absorption pathways.

Exploitation of a rod-shaped, acid-labile curcumin-loaded polymeric nanogel system in the treatment of systemic inflammation.

Curcumin is proven to have potent anti-inflammatory activity, but its low water solubility and rapid degradation in physiological conditions limit its clinical use, particularly in intravenous drug delivery. In this study, we fabricated rod-shaped, acid-labile nanogels, using high biosafe and biocompatible polymers, for intravenous application in systemic inflammation treatment. The constituent polymers of the nanogels were prepared via the conjugation of vitamin B6 derivatives, including pyridoxal and pyridoxamine, onto poly(glutamate) with ester bonds. The aldehyde groups of the pyridoxal and amine groups of the pyridoxamine on the polymers enable crosslinking using a Schiff base during the solvent evaporation procedure for the preparation of the rod-shaped nanogels. Our study is the first to introduce this linkage, which is generated from two vitamin B6 derivatives into a nanogel system. It is also the first to fabricate a rod-shaped nanogel system via simple solvent evaporation. Under acidic conditions, such as those encountered in the endosomes and lysosomes within inflammatory macrophage cells spread in the whole body, imine bonds are cleaved and release payloads. The nanogel polymers were successfully synthesized and characterized, and the formation and disappearance of the Schiff base under neutral and acidic conditions were also confirmed using Fourier transform infrared spectroscopy. Following curcumin encapsulation, the long, rod-shaped nanogels were able to rapidly internalize into macrophage cells in static or adhere to cells under the flows, release their payloads in the acid milieus, and, thus, mitigate curcumin degradation. Consequently, curcumin-loaded, rod-shaped nanogels displayed exceptional anti-inflammatory activity both in vitro and in vivo, by efficiently inhibiting pro-inflammatory mediator secretion. These results demonstrate the feasibility of our acid-labile, rod-shaped nanogels for the treatment of systemic inflammation.

Preparation and optimization of poly (lactic-co-glycolic acid) rod-shaped particles in nano size range for paclitaxel delivery.

Nanoparticle shape has been acknowledged as an important design parameter due to its influence on nanoparticle interaction with biological systems. However, there is lacking of simple and scalable preparation technique for drug loaded non-spherical polymeric nanoparticles for a long time, thus hindering the potential applications. Although our previous research has modified the traditional emulsion solvent evaporation technique by adding guest molecules to prepare non-spherical poly (lactic-co-glycolic acid) (PLGA) particles, it is difficult to obtain nano-sized rods with minor axis less than 200 nm, which may have great potential in cancer therapy. Herein, in present research, the two-step ESE method was used and optimized to prepare poly (lactic-co-glycolic acid) nanorods for paclitaxel delivery. Firstly, the single-factor experiment was used to screen the influence of multi-factors including type of guest molecules, concentration of guest molecules, emulsification method, surfactant concentration, oil volume, poly (lactic-co-glycolic acid) concentration on the size and shape to determine the range of variables; based on the above range, a multi-factor and multi-level orthogonal experiment was designed. The formula is evaluated by the rod fabrication yield and the aspect ratio of major axis to minor axis. The results showed that the yield of nanorods in the optimal formula was 99% and the aspect ratio was 5.35 ± 2.05 with the minor axis of 135.49 ± 72.66 nm, and major axis of 657.77 ± 307.63 nm. In addition, the anti-cancer drug paclitaxel was successfully encapsulated in PLGA nanorods by the same technique. Our results not only enrich the ESE technique for preparing small sized poly (lactic-co-glycolic acid) nanorods, but also envision the potential application of nanorods for targeted cancer therapy with the delivery of paclitaxel.

Removal of Cu2+ metal ions from water using Mg-Fe layered double hydroxide and Mg-Fe LDH/5-(3-nitrophenyllazo)-6-aminouracil nanocomposite for enhancing adsorption properties.

Herein, a new adsorbent was prepared by modifying Mg-Fe LDH for the removal of Cu2+ metal ions from wastewater. Mg-Fe LDH with 5-(3-nitrophenyllazo)-6-aminouracil ligand has been successfully prepared using direct co-precipitation methods and was fully characterized using FTIR analysis, X-ray diffraction, BET surface area theory, zeta potential, partial size, TGA/DTA, CHN, EDX, FESEM, and HRTEM. The surface areas of Mg-Fe LDH and Mg-Fe LDH/ligand were 73.9 m2/g and 34.7 m2/g respectively. Moreover, Cu2+ adsorption on LDH surfaces was intensively examined by adjusting different parameters like time, adsorbent dosage, pH, and Cu2+ metal ion concentration. Several isotherm and kinetic models were investigated to understand the mechanism of adsorption towards Cu2+ metal ions. Adsorption capacity values of LDH and ligand-LDH rounded about 165 and 425 mg/g respectively, applying nonlinear fitting of Freundlich and Langmuir isotherm equations showing that the ligand-LDH can be considered a potential material to produce efficient adsorbent for removal of heavy metal from polluted water. The adsorption of Cu2+ metal ions followed a mixed 1,2-order mechanism. The isoelectric point (PZC) of the prepared sample was investigated and discussed. The effect of coexisting cations on the removal efficiency of Cu2+ ions shows a minor decrease in the adsorption efficiency. Recyclability and chemical stability of these adsorbents show that using Mg-Fe LDH/ligand has an efficiency removal for Cu2+ ions higher than Mg-Fe LDH through seven adsorption/desorption cycles. Moreover, the recycling of the Cu2+ ions was tested using cyclic voltammetry technique from a neutral medium, and the Cu2+ ion recovery was 68%.

Rod-shape MSN@MoS2 Nanoplatform for FL/MSOT/CT Imaging-Guided Photothermal and Photodynamic Therapy.

Rod-shape nanoplatform have received tremendous attention owing to their enhanced ability for cell internalization and high capacity for drug loading. MoS2, widely used in electronic devices, electrocatalysis, sensor and energy-storage, has been studied as photothermal agents over the years. However, the efficacy of rod-shape MoS2 based photothermal agents for photothermal therapy has not been studied before. Here, a near-infrared (NIR) light-absorbing MoS2 nanosheets coated mesoporous silica nanorods with human serum albumin (HSA) modifying and Ce6 loading (MSNR@MoS2-HSA/Ce6) were constructed for combined photothermal and photodynamic therapy. Methods: The near-infrared (NIR) light was used to trigger the synergistic anti-tumor therapy. In addition, breast cancer cell line was applied to evaluate the in vitro anti-tumor activity. The multi-modal imaging capacity and tumor-killing efficiency of the designed nanocomposites in vivo was also demonstrated with the 4T1 tumor-bearing mouse model. Results: These nanocomposites could not only perform NIR light triggered photodynamic therapy (PDT) and photothermal therapy (PTT), but also achieve in vivo fluorescence (FL) /multispectral optical tomography (MSOT)/X-ray computed tomography (CT) triple-model bioimaging. What's more, the rod-shape nanoplatform could be endowed with better anti-tumor ability based on the EPR effect and HSA-mediated active tumor targeting. At the same time, the hyperthermia generated by MoS2 could synergistically improve the PDT effect with the acceleration of the blood flow, leading to the increase of the oxygen level in tumor tissue. Conclusion: MSNR@MoS2-HSA/Ce6 proves to be a promising multi-functional nanoplatform for effective treatment of tumor.

STED Direct Laser Writing of 45 nm Width Nanowire.

Controlled fabrication of 45 nm width nanowire using simulated emission depletion (STED) direct laser writing with a rod-shape effective focus spot is presented. In conventional STED direct laser writing, normally a donut-shaped depletion focus is used, and the minimum linewidth is restricted to 55 nm. In this work, we push this limit to sub-50 nm dimension with a rod-shape effective focus spot, which is the combination of a Gaussian excitation focus and twin-oval depletion focus. Effects of photoinitiator type, excitation laser power, and depletion laser power on the width of the nanowire are explored, respectively. Single nanowire with 45 nm width is obtained, which is λ/18 of excitation wavelength and the minimum linewidth in pentaerythritol triacrylate (PETA) photoresist. Our result accelerates the progress of achievable linewidth reduction in STED direct laser writing.

Cancer Cell Membrane-Camouflaged Nanorods with Endoplasmic Reticulum Targeting for Improved Antitumor Therapy.

Cell membrane-coated nanocarriers have been developed for drug delivery due to their enhanced blood circulation and tissue targeting capacities; however, previous works have generally focused on spherical nanoparticles and extracellular barriers. Many living organisms with different shapes, such as rod-shaped bacilli and rhabdovirus, display different functionalities regarding tissue penetration, cellular uptake, and intracellular distribution. Herein, we developed cancer cell membrane (CCM)-coated nanoparticles with spherical and rod shapes. CCM-coated nanorods (CRs) showed superior endocytosis efficiency compared with their spherical counterparts (CCM-coated nanospheres, CSs) due to the caveolin-mediated pathway. Moreover, CRs can effectively accumulate in the endoplasmic reticulum (ER) region and ship the loaded DOX to the nucleus at a considerable concentration, resulting in ER stress and subsequent apoptosis. After intravenous injection into human pancreatic adenocarcinoma cell (BxPC-3) and pancreatic stellate cell (HPSC) hybrid tumor-bearing nude mice, CRs exhibited improved immune escape ability, rapid extracellular matrix (ECM) penetration (8.2-fold higher than CSs), and enhanced tumor accumulation, further contributing to the enhanced antitumor efficacy. These findings may actually suggest the significance of shape design in improving current cell membrane-based drug delivery systems for effective subcellular targets and tumor therapy.

Sensitivity of Deinococcus grandis rodZ deletion mutant to calcium ions results in enhanced spheroplast size.

RodZ is a cytoskeletal protein associated with bacterial cell shape. It is a transmembrane protein located on the plasma membrane, and it binds to another cytoskeletal protein MreB. Deinococcus grandis contains a rodZ homolog. Although D. grandis is rod-shaped, it becomes spherical in shape when the rodZ homolog is disrupted. The rodZ deletion mutant was treated with lysozyme to generate spheroplasts. The spheroplasts enlarged in medium containing calcium chloride and penicillin. The rodZ deletion mutant spheroplasts were more sensitive to calcium ions than wild type. Cell and cytoplasm sizes of enlarged spheroplasts of the rodZ deletion mutant tended to be larger than those of wild type. Thus, disruption of rodZ enhances plasma and outer membrane expansion in D. grandis spheroplasts.

Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape.

In most well-studied rod-shaped bacteria, peptidoglycan is primarily crosslinked by penicillin-binding proteins (PBPs). However, in mycobacteria, crosslinks formed by L,D-transpeptidases (LDTs) are highly abundant. To elucidate the role of these unusual crosslinks, we characterized Mycobacterium smegmatis cells lacking all LDTs. We find that crosslinks generate by LDTs are required for rod shape maintenance specifically at sites of aging cell wall, a byproduct of polar elongation. Asymmetric polar growth leads to a non-uniform distribution of these two types of crosslinks in a single cell. Consequently, in the absence of LDT-mediated crosslinks, PBP-catalyzed crosslinks become more important. Because of this, Mycobacterium tuberculosis (Mtb) is more rapidly killed using a combination of drugs capable of PBP- and LDT- inhibition. Thus, knowledge about the spatial and genetic relationship between drug targets can be exploited to more effectively treat this pathogen.